---
_id: '8353'
abstract:
- lang: eng
text: "Mrp (Multi resistance and pH adaptation) are broadly distributed secondary
active antiporters that catalyze the transport of monovalent ions such as sodium
and potassium outside of the cell coupled to the inward translocation of protons.
Mrp antiporters are unique in a way that they are composed of seven subunits (MrpABCDEFG)
encoded in a single operon, whereas other antiporters catalyzing the same reaction
are mostly encoded by a single gene. Mrp exchangers are crucial for intracellular
pH homeostasis and Na+ efflux, essential mechanisms for H+ uptake under alkaline
environments and for reduction of the intracellular concentration of toxic cations.
Mrp displays no homology to any other monovalent Na+(K+)/H+ antiporters but Mrp
subunits have primary sequence similarity to essential redox-driven proton pumps,
such as respiratory complex I and membrane-bound hydrogenases. This similarity
reinforces the hypothesis that these present day redox-driven proton pumps are
descended from the Mrp antiporter. The Mrp structure serves as a model to understand
the yet obscure coupling mechanism between ion or electron transfer and proton
translocation in this large group of proteins. In the thesis, I am presenting
the purification, biochemical analysis, cryo-EM analysis and molecular structure
of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å
resolution. Numerous conditions were screened to purify Mrp to high homogeneity
and to obtain an appropriate distribution of single particles on cryo-EM grids
covered with a continuous layer of ultrathin carbon. A preferred particle orientation
problem was solved by performing a tilted data collection. The activity assays
showed the specific pH-dependent\r\nprofile of secondary active antiporters. The
molecular structure shows that Mrp is a dimer of seven-subunit protomers with
50 trans-membrane helices each. The dimer interface is built by many short and
tilted transmembrane helices, probably causing a thinning of the bacterial membrane.
The surface charge distribution shows an extraordinary asymmetry within each monomer,
revealing presumable proton and sodium translocation pathways. The two largest\r\nand
homologous Mrp subunits MrpA and MrpD probably translocate one proton each into
the cell. The sodium ion is likely being translocated in the opposite direction
within the small subunits along a ladder of charged and conserved residues. Based
on the structure, we propose a mechanism were the antiport activity is accomplished
via electrostatic interactions between the charged cations and key charged residues.
The flexible key TM helices coordinate these\r\nelectrostatic interactions, while
the membrane thinning between the monomers enables the translocation of sodium
across the charged membrane. The entire family of redox-driven proton pumps is
likely to perform their mechanism in a likewise manner."
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: ScienComp
acknowledgement: "I acknowledge the scientific service units of the IST Austria for
providing resources by the Life Science Facility, the Electron Microscopy Facility
and the high-performance computer cluster. Special thanks to the cryo-EM specialists
Valentin Hodirnau and Daniel Johann Gütl for spending many hours with me in front
of the microscope and for supporting me to collect the data presented here. I also
want to thank Professor Masahiro Ito for providing plasmid DNA\r\nencoding Mrp from
Anoxybacillus flavithermus WK1. I am a recipient of a DOC Fellowship of the Austrian
Academy of Sciences."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julia
full_name: Steiner, Julia
id: 3BB67EB0-F248-11E8-B48F-1D18A9856A87
last_name: Steiner
orcid: 0000-0003-0493-3775
citation:
ama: Steiner J. Biochemical and structural investigation of the Mrp antiporter,
an ancestor of complex I. 2020. doi:10.15479/AT:ISTA:8353
apa: Steiner, J. (2020). Biochemical and structural investigation of the Mrp
antiporter, an ancestor of complex I. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:8353
chicago: Steiner, Julia. “Biochemical and Structural Investigation of the Mrp Antiporter,
an Ancestor of Complex I.” Institute of Science and Technology Austria, 2020.
https://doi.org/10.15479/AT:ISTA:8353.
ieee: J. Steiner, “Biochemical and structural investigation of the Mrp antiporter,
an ancestor of complex I,” Institute of Science and Technology Austria, 2020.
ista: Steiner J. 2020. Biochemical and structural investigation of the Mrp antiporter,
an ancestor of complex I. Institute of Science and Technology Austria.
mla: Steiner, Julia. Biochemical and Structural Investigation of the Mrp Antiporter,
an Ancestor of Complex I. Institute of Science and Technology Austria, 2020,
doi:10.15479/AT:ISTA:8353.
short: J. Steiner, Biochemical and Structural Investigation of the Mrp Antiporter,
an Ancestor of Complex I, Institute of Science and Technology Austria, 2020.
date_created: 2020-09-09T14:27:01Z
date_published: 2020-09-09T00:00:00Z
date_updated: 2023-09-07T13:14:09Z
day: '09'
ddc:
- '572'
degree_awarded: PhD
department:
- _id: LeSa
doi: 10.15479/AT:ISTA:8353
file:
- access_level: open_access
checksum: 2388d7e6e7a4d364c096fa89f305c3de
content_type: application/pdf
creator: jsteiner
date_created: 2020-09-09T14:22:35Z
date_updated: 2021-09-16T12:40:56Z
file_id: '8354'
file_name: Thesis_Julia_Steiner_pdfA.pdf
file_size: 117547589
relation: main_file
- access_level: closed
checksum: ba112f957b7145462d0ab79044873ee9
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: jsteiner
date_created: 2020-09-09T14:23:25Z
date_updated: 2020-09-15T08:48:37Z
file_id: '8355'
file_name: Thesis_Julia_Steiner.docx
file_size: 223328668
relation: source_file
file_date_updated: 2021-09-16T12:40:56Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: None
page: '191'
project:
- _id: 26169496-B435-11E9-9278-68D0E5697425
grant_number: '24741'
name: Revealing the functional mechanism of Mrp antiporter, an ancestor of complex
I
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '8284'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
title: Biochemical and structural investigation of the Mrp antiporter, an ancestor
of complex I
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8579'
abstract:
- lang: eng
text: Copper (Cu) is an essential trace element for all living organisms and used
as cofactor in key enzymes of important biological processes, such as aerobic
respiration or superoxide dismutation. However, due to its toxicity, cells have
developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for
cuproprotein biogenesis with the need to remove excess Cu. This review summarizes
our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative
bacteria and describes the multiple strategies that bacteria use for uptake, storage
and export of Cu. We furthermore describe general mechanistic principles that
aid the bacterial response to toxic Cu concentrations and illustrate dedicated
Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress
in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu
quota for cell proliferation is of particular importance for microbial pathogens
because Cu is utilized by the host immune system for attenuating pathogen survival
in host cells.
article_number: '242'
article_processing_charge: No
article_type: original
author:
- first_name: Andreea
full_name: Andrei, Andreea
last_name: Andrei
- first_name: Yavuz
full_name: Öztürk, Yavuz
last_name: Öztürk
- first_name: Bahia
full_name: Khalfaoui-Hassani, Bahia
last_name: Khalfaoui-Hassani
- first_name: Juna
full_name: Rauch, Juna
last_name: Rauch
- first_name: Dorian
full_name: Marckmann, Dorian
last_name: Marckmann
- first_name: Petru Iulian
full_name: Trasnea, Petru Iulian
id: D560034C-10C4-11EA-ABF4-A4B43DDC885E
last_name: Trasnea
- first_name: Fevzi
full_name: Daldal, Fevzi
last_name: Daldal
- first_name: Hans-Georg
full_name: Koch, Hans-Georg
last_name: Koch
citation:
ama: 'Andrei A, Öztürk Y, Khalfaoui-Hassani B, et al. Cu homeostasis in bacteria:
The ins and outs. Membranes. 2020;10(9). doi:10.3390/membranes10090242'
apa: 'Andrei, A., Öztürk, Y., Khalfaoui-Hassani, B., Rauch, J., Marckmann, D., Trasnea,
P. I., … Koch, H.-G. (2020). Cu homeostasis in bacteria: The ins and outs. Membranes.
MDPI. https://doi.org/10.3390/membranes10090242'
chicago: 'Andrei, Andreea, Yavuz Öztürk, Bahia Khalfaoui-Hassani, Juna Rauch, Dorian
Marckmann, Petru Iulian Trasnea, Fevzi Daldal, and Hans-Georg Koch. “Cu Homeostasis
in Bacteria: The Ins and Outs.” Membranes. MDPI, 2020. https://doi.org/10.3390/membranes10090242.'
ieee: 'A. Andrei et al., “Cu homeostasis in bacteria: The ins and outs,”
Membranes, vol. 10, no. 9. MDPI, 2020.'
ista: 'Andrei A, Öztürk Y, Khalfaoui-Hassani B, Rauch J, Marckmann D, Trasnea PI,
Daldal F, Koch H-G. 2020. Cu homeostasis in bacteria: The ins and outs. Membranes.
10(9), 242.'
mla: 'Andrei, Andreea, et al. “Cu Homeostasis in Bacteria: The Ins and Outs.” Membranes,
vol. 10, no. 9, 242, MDPI, 2020, doi:10.3390/membranes10090242.'
short: A. Andrei, Y. Öztürk, B. Khalfaoui-Hassani, J. Rauch, D. Marckmann, P.I.
Trasnea, F. Daldal, H.-G. Koch, Membranes 10 (2020).
date_created: 2020-09-28T08:59:26Z
date_published: 2020-09-01T00:00:00Z
date_updated: 2023-08-22T09:34:06Z
day: '01'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.3390/membranes10090242
external_id:
isi:
- '000581446000001'
file:
- access_level: open_access
checksum: ceb43d7554e712dea6f36f9287271737
content_type: application/pdf
creator: dernst
date_created: 2020-09-28T11:36:50Z
date_updated: 2020-09-28T11:36:50Z
file_id: '8583'
file_name: 2020_Membranes_Andrei.pdf
file_size: 4612258
relation: main_file
success: 1
file_date_updated: 2020-09-28T11:36:50Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Membranes
publication_identifier:
eissn:
- '20770375'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Cu homeostasis in bacteria: The ins and outs'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2020'
...
---
_id: '8581'
abstract:
- lang: eng
text: The majority of adenosine triphosphate (ATP) powering cellular processes in
eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present
the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo,
determined by cryo-electron microscopy. Subunits in the membrane domain are arranged
in the ‘proton translocation cluster’ attached to the c-ring and a more distant
‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to
a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation
pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM
maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled
c-ring, suggesting permeability transition pore opening. We propose a model for
the permeability transition pore opening, whereby subunit e pulls the lipid plug
out of the c-ring. Our structure will allow the design of drugs for many emerging
applications in medicine.
acknowledged_ssus:
- _id: EM-Fac
- _id: ScienComp
acknowledgement: We thank J. Novacek from CEITEC (Brno, Czech Republic) for assistance
with collecting the FEI Krios dataset and iNEXT for providing access to CEITEC.
We thank the IST Austria EM facility for access and assistance with collecting the
FEI Glacios dataset. Data processing was performed at the IST high-performance computing
cluster. This work has been supported by iNEXT EM HEDC (proposal 4506), funded by
the Horizon 2020 Programme of the European Commission.
article_processing_charge: No
article_type: original
author:
- first_name: Gergely
full_name: Pinke, Gergely
id: 4D5303E6-F248-11E8-B48F-1D18A9856A87
last_name: Pinke
- first_name: Long
full_name: Zhou, Long
id: 3E751364-F248-11E8-B48F-1D18A9856A87
last_name: Zhou
orcid: 0000-0002-1864-8951
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Pinke G, Zhou L, Sazanov LA. Cryo-EM structure of the entire mammalian F-type
ATP synthase. Nature Structural and Molecular Biology. 2020;27(11):1077-1085.
doi:10.1038/s41594-020-0503-8
apa: Pinke, G., Zhou, L., & Sazanov, L. A. (2020). Cryo-EM structure of the
entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology.
Springer Nature. https://doi.org/10.1038/s41594-020-0503-8
chicago: Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of
the Entire Mammalian F-Type ATP Synthase.” Nature Structural and Molecular
Biology. Springer Nature, 2020. https://doi.org/10.1038/s41594-020-0503-8.
ieee: G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian
F-type ATP synthase,” Nature Structural and Molecular Biology, vol. 27,
no. 11. Springer Nature, pp. 1077–1085, 2020.
ista: Pinke G, Zhou L, Sazanov LA. 2020. Cryo-EM structure of the entire mammalian
F-type ATP synthase. Nature Structural and Molecular Biology. 27(11), 1077–1085.
mla: Pinke, Gergely, et al. “Cryo-EM Structure of the Entire Mammalian F-Type ATP
Synthase.” Nature Structural and Molecular Biology, vol. 27, no. 11, Springer
Nature, 2020, pp. 1077–85, doi:10.1038/s41594-020-0503-8.
short: G. Pinke, L. Zhou, L.A. Sazanov, Nature Structural and Molecular Biology
27 (2020) 1077–1085.
date_created: 2020-09-28T08:59:27Z
date_published: 2020-11-01T00:00:00Z
date_updated: 2023-08-22T09:33:09Z
day: '01'
department:
- _id: LeSa
doi: 10.1038/s41594-020-0503-8
external_id:
isi:
- '000569299400004'
pmid:
- '32929284'
intvolume: ' 27'
isi: 1
issue: '11'
language:
- iso: eng
month: '11'
oa_version: None
page: 1077-1085
pmid: 1
publication: Nature Structural and Molecular Biology
publication_identifier:
eissn:
- '15459985'
issn:
- '15459993'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/structure-of-atpase-solved/
scopus_import: '1'
status: public
title: Cryo-EM structure of the entire mammalian F-type ATP synthase
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 27
year: '2020'
...
---
_id: '8737'
abstract:
- lang: eng
text: Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping
by an unknown mechanism. Here, we present cryo-electron microscopy structures
of ovine complex I in five different conditions, including turnover, at resolutions
up to 2.3 to 2.5 angstroms. Resolved water molecules allowed us to experimentally
define the proton translocation pathways. Quinone binds at three positions along
the quinone cavity, as does the inhibitor rotenone that also binds within subunit
ND4. Dramatic conformational changes around the quinone cavity couple the redox
reaction to proton translocation during open-to-closed state transitions of the
enzyme. In the induced deactive state, the open conformation is arrested by the
ND6 subunit. We propose a detailed molecular coupling mechanism of complex I,
which is an unexpected combination of conformational changes and electrostatic
interactions.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
acknowledgement: We thank J. Novacek (CEITEC Brno) and V.-V. Hodirnau (IST Austria)
for their help with collecting cryo-EM datasets. We thank the IST Life Science and
Electron Microscopy Facilities for providing equipment. This work has been supported
by iNEXT,project number 653706, funded by the Horizon 2020 program of the European
Union. This article reflects only the authors’view,and the European Commission is
not responsible for any use that may be made of the information it contains. CIISB
research infrastructure project LM2015043 funded by MEYS CR is gratefully acknowledged
for the financial support of the measurements at the CF Cryo-electron Microscopy
and Tomography CEITEC MU.This project has received funding from the European Union’s
Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant
Agreement no. 665385
article_number: eabc4209
article_processing_charge: No
article_type: original
author:
- first_name: Domen
full_name: Kampjut, Domen
id: 37233050-F248-11E8-B48F-1D18A9856A87
last_name: Kampjut
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Kampjut D, Sazanov LA. The coupling mechanism of mammalian respiratory complex
I. Science. 2020;370(6516). doi:10.1126/science.abc4209
apa: Kampjut, D., & Sazanov, L. A. (2020). The coupling mechanism of mammalian
respiratory complex I. Science. American Association for the Advancement
of Science. https://doi.org/10.1126/science.abc4209
chicago: Kampjut, Domen, and Leonid A Sazanov. “The Coupling Mechanism of Mammalian
Respiratory Complex I.” Science. American Association for the Advancement
of Science, 2020. https://doi.org/10.1126/science.abc4209.
ieee: D. Kampjut and L. A. Sazanov, “The coupling mechanism of mammalian respiratory
complex I,” Science, vol. 370, no. 6516. American Association for the Advancement
of Science, 2020.
ista: Kampjut D, Sazanov LA. 2020. The coupling mechanism of mammalian respiratory
complex I. Science. 370(6516), eabc4209.
mla: Kampjut, Domen, and Leonid A. Sazanov. “The Coupling Mechanism of Mammalian
Respiratory Complex I.” Science, vol. 370, no. 6516, eabc4209, American
Association for the Advancement of Science, 2020, doi:10.1126/science.abc4209.
short: D. Kampjut, L.A. Sazanov, Science 370 (2020).
date_created: 2020-11-08T23:01:23Z
date_published: 2020-10-30T00:00:00Z
date_updated: 2023-08-22T12:35:38Z
day: '30'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1126/science.abc4209
ec_funded: 1
external_id:
isi:
- '000583031800004'
pmid:
- '32972993'
file:
- access_level: open_access
checksum: 658ba90979ca9528a2efdfac8547047a
content_type: application/pdf
creator: lsazanov
date_created: 2020-11-26T18:47:58Z
date_updated: 2020-11-26T18:47:58Z
file_id: '8820'
file_name: Full_manuscript_with_SI_opt_red.pdf
file_size: 7618987
relation: main_file
success: 1
file_date_updated: 2020-11-26T18:47:58Z
has_accepted_license: '1'
intvolume: ' 370'
isi: 1
issue: '6516'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Science
publication_identifier:
eissn:
- '10959203'
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: The coupling mechanism of mammalian respiratory complex I
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 370
year: '2020'
...
---
_id: '9326'
abstract:
- lang: eng
text: The mitochondrial respiratory chain, formed by five protein complexes, utilizes
energy from catabolic processes to synthesize ATP. Complex I, the first and the
largest protein complex of the chain, harvests electrons from NADH to reduce quinone,
while pumping protons across the mitochondrial membrane. Detailed knowledge of
the working principle of such coupled charge-transfer processes remains, however,
fragmentary due to bottlenecks in understanding redox-driven conformational transitions
and their interplay with the hydrated proton pathways. Complex I from Thermus
thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons
from NADH. Here, employing the latest crystal structure of T. thermophilus complex
I, we have used microsecond-scale molecular dynamics simulations to study the
chemo-mechanical coupling between redox changes of the iron–sulfur clusters and
conformational transitions across complex I. First, we identify the redox switches
within complex I, which allosterically couple the dynamics of the quinone binding
pocket to the site of NADH reduction. Second, our free-energy calculations reveal
that the affinity of the quinone, specifically menaquinone, for the binding-site
is higher than that of its reduced, menaquinol forma design essential for menaquinol
release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser
than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup
of the former furnishes stronger binding interactions with the pocket, favoring
menaquinone for charge transport in T. thermophilus. Our computations are consistent
with experimentally validated mutations and hierarchize the key residues into
three functional classes, identifying new mutation targets. Third, long-range
hydrogen-bond networks connecting the quinone-binding site to the transmembrane
subunits are found to be responsible for proton pumping. Put together, the simulations
reveal the molecular design principles linking redox reactions to quinone turnover
to proton translocation in complex I.
article_processing_charge: No
author:
- first_name: Chitrak
full_name: Gupta, Chitrak
last_name: Gupta
- first_name: Umesh
full_name: Khaniya, Umesh
last_name: Khaniya
- first_name: Chun
full_name: Chan, Chun
last_name: Chan
- first_name: Francois
full_name: Dehez, Francois
last_name: Dehez
- first_name: Mrinal
full_name: Shekhar, Mrinal
last_name: Shekhar
- first_name: M. R.
full_name: Gunner, M. R.
last_name: Gunner
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Christophe
full_name: Chipot, Christophe
last_name: Chipot
- first_name: Abhishek
full_name: Singharoy, Abhishek
last_name: Singharoy
citation:
ama: Gupta C, Khaniya U, Chan C, et al. Charge transfer and chemo-mechanical coupling
in respiratory complex I. 2020. doi:10.1021/jacs.9b13450.s002
apa: Gupta, C., Khaniya, U., Chan, C., Dehez, F., Shekhar, M., Gunner, M. R., …
Singharoy, A. (2020). Charge transfer and chemo-mechanical coupling in respiratory
complex I. American Chemical Society. https://doi.org/10.1021/jacs.9b13450.s002
chicago: Gupta, Chitrak, Umesh Khaniya, Chun Chan, Francois Dehez, Mrinal Shekhar,
M. R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Charge
Transfer and Chemo-Mechanical Coupling in Respiratory Complex I.” American Chemical
Society, 2020. https://doi.org/10.1021/jacs.9b13450.s002.
ieee: C. Gupta et al., “Charge transfer and chemo-mechanical coupling in
respiratory complex I.” American Chemical Society, 2020.
ista: Gupta C, Khaniya U, Chan C, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot
C, Singharoy A. 2020. Charge transfer and chemo-mechanical coupling in respiratory
complex I, American Chemical Society, 10.1021/jacs.9b13450.s002.
mla: Gupta, Chitrak, et al. Charge Transfer and Chemo-Mechanical Coupling in
Respiratory Complex I. American Chemical Society, 2020, doi:10.1021/jacs.9b13450.s002.
short: C. Gupta, U. Khaniya, C. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A. Sazanov,
C. Chipot, A. Singharoy, (2020).
date_created: 2021-04-14T12:05:20Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-22T07:49:37Z
day: '20'
department:
- _id: LeSa
doi: 10.1021/jacs.9b13450.s002
main_file_link:
- open_access: '1'
month: '05'
oa: 1
oa_version: Published Version
publisher: American Chemical Society
related_material:
record:
- id: '8040'
relation: used_in_publication
status: public
status: public
title: Charge transfer and chemo-mechanical coupling in respiratory complex I
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7788'
abstract:
- lang: eng
text: Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative
phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly
understood pediatric disorder featuring brain-specific anomalies and early death.
To study the LS pathomechanism, we here compared OXPHOS proteomes between various
Ndufs4−/− mouse tissues. Ndufs4−/− animals displayed significantly lower CI subunit
levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal
muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4
induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction
in other CI subunit levels, and an increase in specific CI assembly factors. Among
the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2,
identical results were obtained in Ndufs4−/− mouse embryonic fibroblasts (MEFs)
and NDUFS4-mutated LS patient cells. Ndufs4−/− MEFs contained active CI in situ
but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex
(CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells,
NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association
to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with
mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830
(NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological
and CI in silico structural analysis, we conclude that absence of NDUFS4 induces
near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes
active CI in Ndufs4−/− mice and LS patient cells, perhaps in concert with mitochondrial
inner membrane lipids.
article_number: '148213'
article_processing_charge: No
article_type: original
author:
- first_name: Merel J.W.
full_name: Adjobo-Hermans, Merel J.W.
last_name: Adjobo-Hermans
- first_name: Ria
full_name: De Haas, Ria
last_name: De Haas
- first_name: Peter H.G.M.
full_name: Willems, Peter H.G.M.
last_name: Willems
- first_name: Aleksandra
full_name: Wojtala, Aleksandra
last_name: Wojtala
- first_name: Sjenet E.
full_name: Van Emst-De Vries, Sjenet E.
last_name: Van Emst-De Vries
- first_name: Jori A.
full_name: Wagenaars, Jori A.
last_name: Wagenaars
- first_name: Mariel
full_name: Van Den Brand, Mariel
last_name: Van Den Brand
- first_name: Richard J.
full_name: Rodenburg, Richard J.
last_name: Rodenburg
- first_name: Jan A.M.
full_name: Smeitink, Jan A.M.
last_name: Smeitink
- first_name: Leo G.
full_name: Nijtmans, Leo G.
last_name: Nijtmans
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Mariusz R.
full_name: Wieckowski, Mariusz R.
last_name: Wieckowski
- first_name: Werner J.H.
full_name: Koopman, Werner J.H.
last_name: Koopman
citation:
ama: 'Adjobo-Hermans MJW, De Haas R, Willems PHGM, et al. NDUFS4 deletion triggers
loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role
for NDUFAF2. Biochimica et Biophysica Acta - Bioenergetics. 2020;1861(8).
doi:10.1016/j.bbabio.2020.148213'
apa: 'Adjobo-Hermans, M. J. W., De Haas, R., Willems, P. H. G. M., Wojtala, A.,
Van Emst-De Vries, S. E., Wagenaars, J. A., … Koopman, W. J. H. (2020). NDUFS4
deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients:
A stabilizing role for NDUFAF2. Biochimica et Biophysica Acta - Bioenergetics.
Elsevier. https://doi.org/10.1016/j.bbabio.2020.148213'
chicago: 'Adjobo-Hermans, Merel J.W., Ria De Haas, Peter H.G.M. Willems, Aleksandra
Wojtala, Sjenet E. Van Emst-De Vries, Jori A. Wagenaars, Mariel Van Den Brand,
et al. “NDUFS4 Deletion Triggers Loss of NDUFA12 in Ndufs4−/− Mice and Leigh Syndrome
Patients: A Stabilizing Role for NDUFAF2.” Biochimica et Biophysica Acta -
Bioenergetics. Elsevier, 2020. https://doi.org/10.1016/j.bbabio.2020.148213.'
ieee: 'M. J. W. Adjobo-Hermans et al., “NDUFS4 deletion triggers loss of
NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for
NDUFAF2,” Biochimica et Biophysica Acta - Bioenergetics, vol. 1861, no.
8. Elsevier, 2020.'
ista: 'Adjobo-Hermans MJW, De Haas R, Willems PHGM, Wojtala A, Van Emst-De Vries
SE, Wagenaars JA, Van Den Brand M, Rodenburg RJ, Smeitink JAM, Nijtmans LG, Sazanov
LA, Wieckowski MR, Koopman WJH. 2020. NDUFS4 deletion triggers loss of NDUFA12
in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2.
Biochimica et Biophysica Acta - Bioenergetics. 1861(8), 148213.'
mla: 'Adjobo-Hermans, Merel J. W., et al. “NDUFS4 Deletion Triggers Loss of NDUFA12
in Ndufs4−/− Mice and Leigh Syndrome Patients: A Stabilizing Role for NDUFAF2.”
Biochimica et Biophysica Acta - Bioenergetics, vol. 1861, no. 8, 148213,
Elsevier, 2020, doi:10.1016/j.bbabio.2020.148213.'
short: M.J.W. Adjobo-Hermans, R. De Haas, P.H.G.M. Willems, A. Wojtala, S.E. Van
Emst-De Vries, J.A. Wagenaars, M. Van Den Brand, R.J. Rodenburg, J.A.M. Smeitink,
L.G. Nijtmans, L.A. Sazanov, M.R. Wieckowski, W.J.H. Koopman, Biochimica et Biophysica
Acta - Bioenergetics 1861 (2020).
date_created: 2020-05-03T22:00:47Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2023-08-21T06:19:18Z
day: '01'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1016/j.bbabio.2020.148213
external_id:
isi:
- '000540842000012'
pmid:
- '32335026'
file:
- access_level: open_access
checksum: a9b152381307cf45fe266a8dc5640388
content_type: application/pdf
creator: dernst
date_created: 2020-05-04T12:25:19Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7798'
file_name: 2020_BBA_Adjobo_Hermans.pdf
file_size: 3826792
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
intvolume: ' 1861'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Biochimica et Biophysica Acta - Bioenergetics
publication_identifier:
eissn:
- '18792650'
issn:
- '00052728'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome
patients: A stabilizing role for NDUFAF2'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 1861
year: '2020'
...
---
_id: '8040'
abstract:
- lang: eng
text: The mitochondrial respiratory chain, formed by five protein complexes, utilizes
energy from catabolic processes to synthesize ATP. Complex I, the first and the
largest protein complex of the chain, harvests electrons from NADH to reduce quinone,
while pumping protons across the mitochondrial membrane. Detailed knowledge of
the working principle of such coupled charge-transfer processes remains, however,
fragmentary due to bottlenecks in understanding redox-driven conformational transitions
and their interplay with the hydrated proton pathways. Complex I from Thermus
thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons
from NADH. Here, employing the latest crystal structure of T. thermophilus complex
I, we have used microsecond-scale molecular dynamics simulations to study the
chemo-mechanical coupling between redox changes of the iron–sulfur clusters and
conformational transitions across complex I. First, we identify the redox switches
within complex I, which allosterically couple the dynamics of the quinone binding
pocket to the site of NADH reduction. Second, our free-energy calculations reveal
that the affinity of the quinone, specifically menaquinone, for the binding-site
is higher than that of its reduced, menaquinol form—a design essential for menaquinol
release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser
than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup
of the former furnishes stronger binding interactions with the pocket, favoring
menaquinone for charge transport in T. thermophilus. Our computations are consistent
with experimentally validated mutations and hierarchize the key residues into
three functional classes, identifying new mutation targets. Third, long-range
hydrogen-bond networks connecting the quinone-binding site to the transmembrane
subunits are found to be responsible for proton pumping. Put together, the simulations
reveal the molecular design principles linking redox reactions to quinone turnover
to proton translocation in complex I.
article_processing_charge: No
article_type: original
author:
- first_name: Chitrak
full_name: Gupta, Chitrak
last_name: Gupta
- first_name: Umesh
full_name: Khaniya, Umesh
last_name: Khaniya
- first_name: Chun Kit
full_name: Chan, Chun Kit
last_name: Chan
- first_name: Francois
full_name: Dehez, Francois
last_name: Dehez
- first_name: Mrinal
full_name: Shekhar, Mrinal
last_name: Shekhar
- first_name: M. R.
full_name: Gunner, M. R.
last_name: Gunner
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Christophe
full_name: Chipot, Christophe
last_name: Chipot
- first_name: Abhishek
full_name: Singharoy, Abhishek
last_name: Singharoy
citation:
ama: Gupta C, Khaniya U, Chan CK, et al. Charge transfer and chemo-mechanical coupling
in respiratory complex I. Journal of the American Chemical Society. 2020;142(20):9220-9230.
doi:10.1021/jacs.9b13450
apa: Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R.,
… Singharoy, A. (2020). Charge transfer and chemo-mechanical coupling in respiratory
complex I. Journal of the American Chemical Society. American Chemical
Society. https://doi.org/10.1021/jacs.9b13450
chicago: Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar,
M. R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Charge
Transfer and Chemo-Mechanical Coupling in Respiratory Complex I.” Journal of
the American Chemical Society. American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450.
ieee: C. Gupta et al., “Charge transfer and chemo-mechanical coupling in
respiratory complex I,” Journal of the American Chemical Society, vol.
142, no. 20. American Chemical Society, pp. 9220–9230, 2020.
ista: Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot
C, Singharoy A. 2020. Charge transfer and chemo-mechanical coupling in respiratory
complex I. Journal of the American Chemical Society. 142(20), 9220–9230.
mla: Gupta, Chitrak, et al. “Charge Transfer and Chemo-Mechanical Coupling in Respiratory
Complex I.” Journal of the American Chemical Society, vol. 142, no. 20,
American Chemical Society, 2020, pp. 9220–30, doi:10.1021/jacs.9b13450.
short: C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A.
Sazanov, C. Chipot, A. Singharoy, Journal of the American Chemical Society 142
(2020) 9220–9230.
date_created: 2020-06-29T07:59:35Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-22T07:49:38Z
day: '20'
department:
- _id: LeSa
doi: 10.1021/jacs.9b13450
external_id:
isi:
- '000537415600020'
pmid:
- '32347721'
intvolume: ' 142'
isi: 1
issue: '20'
language:
- iso: eng
month: '05'
oa_version: None
page: 9220-9230
pmid: 1
publication: Journal of the American Chemical Society
publication_identifier:
eissn:
- '15205126'
issn:
- '00027863'
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
related_material:
record:
- id: '9326'
relation: research_data
status: public
- id: '9713'
relation: research_data
status: public
- id: '9878'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Charge transfer and chemo-mechanical coupling in respiratory complex I
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 142
year: '2020'
...
---
_id: '9713'
abstract:
- lang: eng
text: Additional analyses of the trajectories
article_processing_charge: No
author:
- first_name: Chitrak
full_name: Gupta, Chitrak
last_name: Gupta
- first_name: Umesh
full_name: Khaniya, Umesh
last_name: Khaniya
- first_name: Chun Kit
full_name: Chan, Chun Kit
last_name: Chan
- first_name: Francois
full_name: Dehez, Francois
last_name: Dehez
- first_name: Mrinal
full_name: Shekhar, Mrinal
last_name: Shekhar
- first_name: M.R.
full_name: Gunner, M.R.
last_name: Gunner
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Christophe
full_name: Chipot, Christophe
last_name: Chipot
- first_name: Abhishek
full_name: Singharoy, Abhishek
last_name: Singharoy
citation:
ama: Gupta C, Khaniya U, Chan CK, et al. Supporting information. 2020. doi:10.1021/jacs.9b13450.s001
apa: Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R.,
… Singharoy, A. (2020). Supporting information. American Chemical Society . https://doi.org/10.1021/jacs.9b13450.s001
chicago: Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar,
M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Supporting
Information.” American Chemical Society , 2020. https://doi.org/10.1021/jacs.9b13450.s001.
ieee: C. Gupta et al., “Supporting information.” American Chemical Society
, 2020.
ista: Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot
C, Singharoy A. 2020. Supporting information, American Chemical Society , 10.1021/jacs.9b13450.s001.
mla: Gupta, Chitrak, et al. Supporting Information. American Chemical Society
, 2020, doi:10.1021/jacs.9b13450.s001.
short: C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A.
Sazanov, C. Chipot, A. Singharoy, (2020).
date_created: 2021-07-23T12:02:39Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-22T07:49:38Z
day: '20'
department:
- _id: LeSa
doi: 10.1021/jacs.9b13450.s001
month: '05'
oa_version: Published Version
publisher: 'American Chemical Society '
related_material:
record:
- id: '8040'
relation: used_in_publication
status: public
status: public
title: Supporting information
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '9878'
article_processing_charge: No
author:
- first_name: Chitrak
full_name: Gupta, Chitrak
last_name: Gupta
- first_name: Umesh
full_name: Khaniya, Umesh
last_name: Khaniya
- first_name: Chun Kit
full_name: Chan, Chun Kit
last_name: Chan
- first_name: Francois
full_name: Dehez, Francois
last_name: Dehez
- first_name: Mrinal
full_name: Shekhar, Mrinal
last_name: Shekhar
- first_name: M.R.
full_name: Gunner, M.R.
last_name: Gunner
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Christophe
full_name: Chipot, Christophe
last_name: Chipot
- first_name: Abhishek
full_name: Singharoy, Abhishek
last_name: Singharoy
citation:
ama: Gupta C, Khaniya U, Chan CK, et al. Movies. 2020. doi:10.1021/jacs.9b13450.s002
apa: Gupta, C., Khaniya, U., Chan, C. K., Dehez, F., Shekhar, M., Gunner, M. R.,
… Singharoy, A. (2020). Movies. American Chemical Society. https://doi.org/10.1021/jacs.9b13450.s002
chicago: Gupta, Chitrak, Umesh Khaniya, Chun Kit Chan, Francois Dehez, Mrinal Shekhar,
M.R. Gunner, Leonid A Sazanov, Christophe Chipot, and Abhishek Singharoy. “Movies.”
American Chemical Society, 2020. https://doi.org/10.1021/jacs.9b13450.s002.
ieee: C. Gupta et al., “Movies.” American Chemical Society, 2020.
ista: Gupta C, Khaniya U, Chan CK, Dehez F, Shekhar M, Gunner MR, Sazanov LA, Chipot
C, Singharoy A. 2020. Movies, American Chemical Society, 10.1021/jacs.9b13450.s002.
mla: Gupta, Chitrak, et al. Movies. American Chemical Society, 2020, doi:10.1021/jacs.9b13450.s002.
short: C. Gupta, U. Khaniya, C.K. Chan, F. Dehez, M. Shekhar, M.R. Gunner, L.A.
Sazanov, C. Chipot, A. Singharoy, (2020).
date_created: 2021-08-11T09:18:54Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-22T07:49:38Z
day: '20'
department:
- _id: LeSa
doi: 10.1021/jacs.9b13450.s002
month: '05'
oa_version: Published Version
publisher: American Chemical Society
related_material:
record:
- id: '8040'
relation: used_in_publication
status: public
status: public
title: Movies
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '6919'
article_number: eaaw6490
article_processing_charge: No
author:
- first_name: Chao
full_name: Qi, Chao
last_name: Qi
- first_name: Giulio Di
full_name: Minin, Giulio Di
last_name: Minin
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
- first_name: Anton
full_name: Wutz, Anton
last_name: Wutz
- first_name: Volodymyr M.
full_name: Korkhov, Volodymyr M.
last_name: Korkhov
citation:
ama: Qi C, Minin GD, Vercellino I, Wutz A, Korkhov VM. Structural basis of sterol
recognition by human hedgehog receptor PTCH1. Science Advances. 2019;5(9).
doi:10.1126/sciadv.aaw6490
apa: Qi, C., Minin, G. D., Vercellino, I., Wutz, A., & Korkhov, V. M. (2019).
Structural basis of sterol recognition by human hedgehog receptor PTCH1. Science
Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.aaw6490
chicago: Qi, Chao, Giulio Di Minin, Irene Vercellino, Anton Wutz, and Volodymyr
M. Korkhov. “Structural Basis of Sterol Recognition by Human Hedgehog Receptor
PTCH1.” Science Advances. American Association for the Advancement of Science,
2019. https://doi.org/10.1126/sciadv.aaw6490.
ieee: C. Qi, G. D. Minin, I. Vercellino, A. Wutz, and V. M. Korkhov, “Structural
basis of sterol recognition by human hedgehog receptor PTCH1,” Science Advances,
vol. 5, no. 9. American Association for the Advancement of Science, 2019.
ista: Qi C, Minin GD, Vercellino I, Wutz A, Korkhov VM. 2019. Structural basis of
sterol recognition by human hedgehog receptor PTCH1. Science Advances. 5(9), eaaw6490.
mla: Qi, Chao, et al. “Structural Basis of Sterol Recognition by Human Hedgehog
Receptor PTCH1.” Science Advances, vol. 5, no. 9, eaaw6490, American Association
for the Advancement of Science, 2019, doi:10.1126/sciadv.aaw6490.
short: C. Qi, G.D. Minin, I. Vercellino, A. Wutz, V.M. Korkhov, Science Advances
5 (2019).
date_created: 2019-09-29T22:00:45Z
date_published: 2019-09-18T00:00:00Z
date_updated: 2023-08-30T06:55:31Z
day: '18'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1126/sciadv.aaw6490
external_id:
isi:
- '000491128800062'
file:
- access_level: open_access
checksum: b2256c9117655bc15f621ba0babf219f
content_type: application/pdf
creator: kschuh
date_created: 2019-10-02T11:13:54Z
date_updated: 2020-07-14T12:47:44Z
file_id: '6928'
file_name: 2019_AAAS_Qi.pdf
file_size: 1236101
relation: main_file
file_date_updated: 2020-07-14T12:47:44Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Science Advances
publication_identifier:
eissn:
- '23752548'
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structural basis of sterol recognition by human hedgehog receptor PTCH1
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2019'
...
---
_id: '7395'
abstract:
- lang: eng
text: The mitochondrial electron transport chain complexes are organized into supercomplexes
(SCs) of defined stoichiometry, which have been proposed to regulate electron
flux via substrate channeling. We demonstrate that CoQ trapping in the isolated
SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure,
resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may
be rate limiting because of unequal access of CoQ to the active sites of CIII2.
CI shows a transition between “closed” and “open” conformations, accompanied by
the striking rotation of a key transmembrane helix. Furthermore, the state of
CI affects the conformational flexibility within CIII2, demonstrating crosstalk
between the enzymes. CoQ was identified at only three of the four binding sites
in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally
relevant manner. Together, these observations indicate a more nuanced functional
role for the SCs.
article_processing_charge: No
article_type: original
author:
- first_name: James A
full_name: Letts, James A
id: 322DA418-F248-11E8-B48F-1D18A9856A87
last_name: Letts
orcid: 0000-0002-9864-3586
- first_name: Karol
full_name: Fiedorczuk, Karol
id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
last_name: Fiedorczuk
- first_name: Gianluca
full_name: Degliesposti, Gianluca
last_name: Degliesposti
- first_name: Mark
full_name: Skehel, Mark
last_name: Skehel
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. Structures of
respiratory supercomplex I+III2 reveal functional and conformational crosstalk.
Molecular Cell. 2019;75(6):1131-1146.e6. doi:10.1016/j.molcel.2019.07.022
apa: Letts, J. A., Fiedorczuk, K., Degliesposti, G., Skehel, M., & Sazanov,
L. A. (2019). Structures of respiratory supercomplex I+III2 reveal functional
and conformational crosstalk. Molecular Cell. Cell Press. https://doi.org/10.1016/j.molcel.2019.07.022
chicago: Letts, James A, Karol Fiedorczuk, Gianluca Degliesposti, Mark Skehel, and
Leonid A Sazanov. “Structures of Respiratory Supercomplex I+III2 Reveal Functional
and Conformational Crosstalk.” Molecular Cell. Cell Press, 2019. https://doi.org/10.1016/j.molcel.2019.07.022.
ieee: J. A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, and L. A. Sazanov,
“Structures of respiratory supercomplex I+III2 reveal functional and conformational
crosstalk,” Molecular Cell, vol. 75, no. 6. Cell Press, p. 1131–1146.e6,
2019.
ista: Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA. 2019. Structures
of respiratory supercomplex I+III2 reveal functional and conformational crosstalk.
Molecular Cell. 75(6), 1131–1146.e6.
mla: Letts, James A., et al. “Structures of Respiratory Supercomplex I+III2 Reveal
Functional and Conformational Crosstalk.” Molecular Cell, vol. 75, no.
6, Cell Press, 2019, p. 1131–1146.e6, doi:10.1016/j.molcel.2019.07.022.
short: J.A. Letts, K. Fiedorczuk, G. Degliesposti, M. Skehel, L.A. Sazanov, Molecular
Cell 75 (2019) 1131–1146.e6.
date_created: 2020-01-29T16:02:33Z
date_published: 2019-09-19T00:00:00Z
date_updated: 2023-09-07T14:53:06Z
day: '19'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1016/j.molcel.2019.07.022
ec_funded: 1
external_id:
isi:
- '000486614200006'
pmid:
- '31492636'
file:
- access_level: open_access
checksum: 5202f53a237d6650ece038fbf13bdcea
content_type: application/pdf
creator: dernst
date_created: 2020-02-04T10:37:28Z
date_updated: 2020-07-14T12:47:57Z
file_id: '7447'
file_name: 2019_MolecularCell_Letts.pdf
file_size: 9654895
relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: ' 75'
isi: 1
issue: '6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1131-1146.e6
pmid: 1
project:
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '701309'
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
publication: Molecular Cell
publication_identifier:
issn:
- 1097-2765
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structures of respiratory supercomplex I+III2 reveal functional and conformational
crosstalk
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 75
year: '2019'
...
---
_id: '6352'
abstract:
- lang: eng
text: Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol),
often leads to the development of acute liver failure (ALF). This study aimed
to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on
the onset of liver damage and regeneration dynamics in animals with ALF induced
by acetaminophen, to test the liver protective efficacy of MSCs proteome depending
on the oxygen tension in cell culture, and to blueprint protein components responsible
for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic
(5% and 10% O2) and normal (21% O2) conditions were used to treat ALF induced
in mice by injection of acetaminophen. To test the effect of reduced oxygen tension
in cell culture on resulting MSCs proteome content we applied a combination of
high performance liquid chromatography and mass-spectrometry (LC–MS/MS) for the
identification of proteins in lysates of MSCs cultured at different O2 levels.
The treatment of acetaminophen-administered animals with proteins released from
cultured MSCs resulted in the inhibition of inflammatory reactions in damaged
liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions
obtained from MSCs cultured at lower O2 level were shown to be more potent than
a composition prepared from normoxic cells. A comparative characterization of
protein pattern and identification of individual components done by a cytokine
assay and proteomics analysis of protein compositions revealed that even moderate
hypoxia produces discrete changes in the expression of various subsets of proteins
responsible for intracellular respiration and cell signaling. The application
of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly
accelerates healing process in damaged liver tissue. The proteomics data obtained
for different preparations offer new information about the potential candidates
in the MSCs protein repertoire sensitive to oxygen tension in culture medium,
which can be involved in the generalized mechanisms the cells use to respond to
acute liver failure.
acknowledgement: The studies were supported by the Austrian Federal Ministry of Economy,
Family and Youth through the initiative “Laura Bassi Centres of Expertise” funding
the Center of Optimized Structural Stud-ies, grant No. 253275
article_processing_charge: Yes (via OA deal)
author:
- first_name: Andrey Alexandrovich
full_name: Temnov, Andrey Alexandrovich
last_name: Temnov
- first_name: Konstantin Arkadevich
full_name: Rogov, Konstantin Arkadevich
last_name: Rogov
- first_name: Alla Nikolaevna
full_name: Sklifas, Alla Nikolaevna
last_name: Sklifas
- first_name: Elena Valerievna
full_name: Klychnikova, Elena Valerievna
last_name: Klychnikova
- first_name: Markus
full_name: Hartl, Markus
last_name: Hartl
- first_name: Kristina
full_name: Djinovic-Carugo, Kristina
last_name: Djinovic-Carugo
- first_name: Alexej
full_name: Charnagalov, Alexej
id: 49F06DBA-F248-11E8-B48F-1D18A9856A87
last_name: Charnagalov
citation:
ama: Temnov AA, Rogov KA, Sklifas AN, et al. Protective properties of the cultured
stem cell proteome studied in an animal model of acetaminophen-induced acute liver
failure. Molecular Biology Reports. 2019. doi:10.1007/s11033-019-04765-z
apa: Temnov, A. A., Rogov, K. A., Sklifas, A. N., Klychnikova, E. V., Hartl, M.,
Djinovic-Carugo, K., & Charnagalov, A. (2019). Protective properties of the
cultured stem cell proteome studied in an animal model of acetaminophen-induced
acute liver failure. Molecular Biology Reports. Springer. https://doi.org/10.1007/s11033-019-04765-z
chicago: Temnov, Andrey Alexandrovich, Konstantin Arkadevich Rogov, Alla Nikolaevna
Sklifas, Elena Valerievna Klychnikova, Markus Hartl, Kristina Djinovic-Carugo,
and Alexej Charnagalov. “Protective Properties of the Cultured Stem Cell Proteome
Studied in an Animal Model of Acetaminophen-Induced Acute Liver Failure.” Molecular
Biology Reports. Springer, 2019. https://doi.org/10.1007/s11033-019-04765-z.
ieee: A. A. Temnov et al., “Protective properties of the cultured stem cell
proteome studied in an animal model of acetaminophen-induced acute liver failure,”
Molecular Biology Reports. Springer, 2019.
ista: Temnov AA, Rogov KA, Sklifas AN, Klychnikova EV, Hartl M, Djinovic-Carugo
K, Charnagalov A. 2019. Protective properties of the cultured stem cell proteome
studied in an animal model of acetaminophen-induced acute liver failure. Molecular
Biology Reports.
mla: Temnov, Andrey Alexandrovich, et al. “Protective Properties of the Cultured
Stem Cell Proteome Studied in an Animal Model of Acetaminophen-Induced Acute Liver
Failure.” Molecular Biology Reports, Springer, 2019, doi:10.1007/s11033-019-04765-z.
short: A.A. Temnov, K.A. Rogov, A.N. Sklifas, E.V. Klychnikova, M. Hartl, K. Djinovic-Carugo,
A. Charnagalov, Molecular Biology Reports (2019).
date_created: 2019-04-28T21:59:14Z
date_published: 2019-04-12T00:00:00Z
date_updated: 2023-08-25T10:14:26Z
day: '12'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1007/s11033-019-04765-z
external_id:
isi:
- '000470332600049'
file:
- access_level: open_access
checksum: 45bf040bbce1cea274f6013fa18ba21b
content_type: application/pdf
creator: dernst
date_created: 2019-04-30T09:52:36Z
date_updated: 2020-07-14T12:47:28Z
file_id: '6362'
file_name: 2019_MolecularBioReport_Temnov.pdf
file_size: 1948014
relation: main_file
file_date_updated: 2020-07-14T12:47:28Z
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: Molecular Biology Reports
publication_identifier:
eissn:
- '15734978'
issn:
- '03014851'
publication_status: published
publisher: Springer
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protective properties of the cultured stem cell proteome studied in an animal
model of acetaminophen-induced acute liver failure
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
year: '2019'
...
---
_id: '6848'
abstract:
- lang: eng
text: Proton-translocating transhydrogenase (also known as nicotinamide nucleotide
transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner
mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride
between NADH and NADP+, coupled to the translocation of one proton across the
membrane. Its main physiological function is the generation of NADPH, which is
a substrate in anabolic reactions and a regulator of oxidative status; however,
NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid
deficiency in humans and metabolic abnormalities in mice, similar to those observed
in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve
a rotation of around 180° of the entire NADP(H)-binding domain that alternately
participates in hydride transfer and proton-channel gating. However, owing to
the lack of high-resolution structures of intact NNT, the details of this process
remain unclear5,6. Here we present the cryo-electron microscopy structure of intact
mammalian NNT in different conformational states. We show how the NADP(H)-binding
domain opens the proton channel to the opposite sides of the membrane, and we
provide structures of these two states. We also describe the catalytically important
interfaces and linkers between the membrane and the soluble domains and their
roles in nucleotide exchange. These structures enable us to propose a revised
mechanism for a coupling process in NNT that is consistent with a large body of
previous biochemical work. Our results are relevant to the development of currently
unavailable NNT inhibitors, which may have therapeutic potential in ischaemia
reperfusion injury, metabolic syndrome and some cancers7,8,9.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: " We thank R. Thompson, G. Effantin and V.-V. Hodirnau for their
assistance with collecting NADP+, NADPH and apo datasets, respectively. Data processing
was performed at the IST high-performance computing cluster.\r\nThis project has
received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement no. 665385."
article_processing_charge: No
article_type: letter_note
author:
- first_name: Domen
full_name: Kampjut, Domen
id: 37233050-F248-11E8-B48F-1D18A9856A87
last_name: Kampjut
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating
transhydrogenase. Nature. 2019;573(7773):291–295. doi:10.1038/s41586-019-1519-2
apa: Kampjut, D., & Sazanov, L. A. (2019). Structure and mechanism of mitochondrial
proton-translocating transhydrogenase. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1519-2
chicago: Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial
Proton-Translocating Transhydrogenase.” Nature. Springer Nature, 2019.
https://doi.org/10.1038/s41586-019-1519-2.
ieee: D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating
transhydrogenase,” Nature, vol. 573, no. 7773. Springer Nature, pp. 291–295,
2019.
ista: Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating
transhydrogenase. Nature. 573(7773), 291–295.
mla: Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial
Proton-Translocating Transhydrogenase.” Nature, vol. 573, no. 7773, Springer
Nature, 2019, pp. 291–295, doi:10.1038/s41586-019-1519-2.
short: D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295.
date_created: 2019-09-04T06:21:41Z
date_published: 2019-09-12T00:00:00Z
date_updated: 2024-03-25T23:30:08Z
day: '12'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41586-019-1519-2
ec_funded: 1
external_id:
isi:
- '000485415400061'
pmid:
- '31462775'
file:
- access_level: open_access
checksum: 52728cda5210a3e9b74cc204e8aed3d5
content_type: application/pdf
creator: lsazanov
date_created: 2020-11-26T16:33:44Z
date_updated: 2020-11-26T16:33:44Z
file_id: '8821'
file_name: Manuscript_final_acc_withFigs_SI_opt_red.pdf
file_size: 3066206
relation: main_file
success: 1
file_date_updated: 2020-11-26T16:33:44Z
has_accepted_license: '1'
intvolume: ' 573'
isi: 1
issue: '7773'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 291–295
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/
record:
- id: '8340'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Structure and mechanism of mitochondrial proton-translocating transhydrogenase
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 573
year: '2019'
...
---
_id: '6859'
abstract:
- lang: eng
text: V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found
in archaeaand eubacteria, couple ATP hydrolysis or synthesis to proton translocation
across theplasma membrane using the rotary-catalysis mechanism. They belong to
the V-typeATPase family, which differs from the mitochondrial/chloroplast F-type
ATP synthasesin overall architecture. We solved cryo–electron microscopy structures
of the intactThermus thermophilusV/A-ATPase, reconstituted into lipid nanodiscs,
in three rotationalstates and two substates. These structures indicate substantial
flexibility betweenV1and Voin a working enzyme, which results from mechanical
competition between centralshaft rotation and resistance from the peripheral stalks.
We also describedetails of adenosine diphosphate inhibition release, V1-Votorque
transmission, andproton translocation, which are relevant for the entire V-type
ATPase family.
acknowledged_ssus:
- _id: ScienComp
article_number: eaaw9144
article_processing_charge: No
author:
- first_name: Long
full_name: Zhou, Long
id: 3E751364-F248-11E8-B48F-1D18A9856A87
last_name: Zhou
orcid: 0000-0002-1864-8951
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Zhou L, Sazanov LA. Structure and conformational plasticity of the intact Thermus
thermophilus V/A-type ATPase. Science. 2019;365(6455). doi:10.1126/science.aaw9144
apa: Zhou, L., & Sazanov, L. A. (2019). Structure and conformational plasticity
of the intact Thermus thermophilus V/A-type ATPase. Science. AAAS. https://doi.org/10.1126/science.aaw9144
chicago: Zhou, Long, and Leonid A Sazanov. “Structure and Conformational Plasticity
of the Intact Thermus Thermophilus V/A-Type ATPase.” Science. AAAS, 2019.
https://doi.org/10.1126/science.aaw9144.
ieee: L. Zhou and L. A. Sazanov, “Structure and conformational plasticity of the
intact Thermus thermophilus V/A-type ATPase,” Science, vol. 365, no. 6455.
AAAS, 2019.
ista: Zhou L, Sazanov LA. 2019. Structure and conformational plasticity of the intact
Thermus thermophilus V/A-type ATPase. Science. 365(6455), eaaw9144.
mla: Zhou, Long, and Leonid A. Sazanov. “Structure and Conformational Plasticity
of the Intact Thermus Thermophilus V/A-Type ATPase.” Science, vol. 365,
no. 6455, eaaw9144, AAAS, 2019, doi:10.1126/science.aaw9144.
short: L. Zhou, L.A. Sazanov, Science 365 (2019).
date_created: 2019-09-07T19:04:45Z
date_published: 2019-08-23T00:00:00Z
date_updated: 2023-08-29T07:52:02Z
day: '23'
department:
- _id: LeSa
doi: 10.1126/science.aaw9144
external_id:
isi:
- '000482464000043'
pmid:
- '31439765'
intvolume: ' 365'
isi: 1
issue: '6455'
language:
- iso: eng
month: '08'
oa_version: None
pmid: 1
publication: Science
publication_identifier:
eissn:
- 1095-9203
issn:
- 0036-8075
publication_status: published
publisher: AAAS
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/structure-of-protein-nano-turbine-revealed/
scopus_import: '1'
status: public
title: Structure and conformational plasticity of the intact Thermus thermophilus
V/A-type ATPase
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 365
year: '2019'
...
---
_id: '152'
abstract:
- lang: eng
text: Complex I has an essential role in ATP production by coupling electron transfer
from NADH to quinone with translocation of protons across the inner mitochondrial
membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited
diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative
conditions. Until recently, the understanding of complex I deficiency on the molecular
level was limited due to the lack of high-resolution structures of the enzyme.
However, due to developments in single particle cryo-electron microscopy (cryo-EM),
recent studies have reported nearly atomic resolution maps and models of mitochondrial
complex I. These structures significantly add to our understanding of complex
I mechanism and assembly. The disease-causing mutations are discussed here in
their structural context.
article_processing_charge: No
article_type: original
author:
- first_name: Karol
full_name: Fiedorczuk, Karol
id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
last_name: Fiedorczuk
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Fiedorczuk K, Sazanov LA. Mammalian mitochondrial complex I structure and disease
causing mutations. Trends in Cell Biology. 2018;28(10):835-867. doi:10.1016/j.tcb.2018.06.006
apa: Fiedorczuk, K., & Sazanov, L. A. (2018). Mammalian mitochondrial complex
I structure and disease causing mutations. Trends in Cell Biology. Elsevier.
https://doi.org/10.1016/j.tcb.2018.06.006
chicago: Fiedorczuk, Karol, and Leonid A Sazanov. “Mammalian Mitochondrial Complex
I Structure and Disease Causing Mutations.” Trends in Cell Biology. Elsevier,
2018. https://doi.org/10.1016/j.tcb.2018.06.006.
ieee: K. Fiedorczuk and L. A. Sazanov, “Mammalian mitochondrial complex I structure
and disease causing mutations,” Trends in Cell Biology, vol. 28, no. 10.
Elsevier, pp. 835–867, 2018.
ista: Fiedorczuk K, Sazanov LA. 2018. Mammalian mitochondrial complex I structure
and disease causing mutations. Trends in Cell Biology. 28(10), 835–867.
mla: Fiedorczuk, Karol, and Leonid A. Sazanov. “Mammalian Mitochondrial Complex
I Structure and Disease Causing Mutations.” Trends in Cell Biology, vol.
28, no. 10, Elsevier, 2018, pp. 835–67, doi:10.1016/j.tcb.2018.06.006.
short: K. Fiedorczuk, L.A. Sazanov, Trends in Cell Biology 28 (2018) 835–867.
date_created: 2018-12-11T11:44:54Z
date_published: 2018-07-26T00:00:00Z
date_updated: 2023-09-13T08:51:56Z
day: '26'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1016/j.tcb.2018.06.006
external_id:
isi:
- '000445118200007'
file:
- access_level: open_access
checksum: ef6d2b4e1fd63948539639242610bfa6
content_type: application/pdf
creator: lsazanov
date_created: 2019-11-07T12:55:20Z
date_updated: 2020-07-14T12:45:00Z
file_id: '6994'
file_name: SasanovFinalMS+EdComments_LS_allacc_withFigs.pdf
file_size: 2185385
relation: main_file
file_date_updated: 2020-07-14T12:45:00Z
has_accepted_license: '1'
intvolume: ' 28'
isi: 1
issue: '10'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Submitted Version
page: 835 - 867
publication: Trends in Cell Biology
publication_status: published
publisher: Elsevier
publist_id: '7769'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mammalian mitochondrial complex I structure and disease causing mutations
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 28
year: '2018'
...
---
_id: '444'
abstract:
- lang: eng
text: Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular
energy generation, contributing to the proton motive force used to produce ATP.
It couples the transfer of two electrons between NADH and quinone to translocation
of four protons across the membrane. It is the largest protein assembly of bacterial
and mitochondrial respiratory chains, composed, in mammals, of up to 45 subunits
with a total molecular weight of ∼1 MDa. Bacterial enzyme is about half the size,
providing the important “minimal” model of complex I. The l-shaped complex consists
of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where
proton translocation takes place. Previously, we have solved the crystal structures
of the hydrophilic domain of complex I from Thermus thermophilus and of the membrane
domain from Escherichia coli, followed by the atomic structure of intact, entire
complex I from T. thermophilus. Recently, we have solved by cryo-EM a first complete
atomic structure of mammalian (ovine) mitochondrial complex I. Core subunits are
well conserved from the bacterial version, whilst supernumerary subunits form
an interlinked, stabilizing shell around the core. Subunits containing additional
cofactors, including Zn ion, NADPH and phosphopantetheine, probably have regulatory
roles. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative
diseases. The structure of mammalian enzyme provides many insights into complex
I mechanism, assembly, maturation and dysfunction, allowing detailed molecular
analysis of disease-causing mutations.
author:
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: 'Sazanov LA. Structure of respiratory complex I: “Minimal” bacterial and “de
luxe” mammalian versions. In: Wikström M, ed. Mechanisms of Primary Energy
Transduction in Biology . Mechanisms of Primary Energy Transduction in Biology
. Royal Society of Chemistry; 2017:25-59. doi:10.1039/9781788010405-00025'
apa: 'Sazanov, L. A. (2017). Structure of respiratory complex I: “Minimal” bacterial
and “de luxe” mammalian versions. In M. Wikström (Ed.), Mechanisms of primary
energy transduction in biology (pp. 25–59). Royal Society of Chemistry. https://doi.org/10.1039/9781788010405-00025'
chicago: 'Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial
and ‘de Luxe’ Mammalian Versions.” In Mechanisms of Primary Energy Transduction
in Biology , edited by Mårten Wikström, 25–59. Mechanisms of Primary Energy
Transduction in Biology . Royal Society of Chemistry, 2017. https://doi.org/10.1039/9781788010405-00025.'
ieee: 'L. A. Sazanov, “Structure of respiratory complex I: ‘Minimal’ bacterial and
‘de luxe’ mammalian versions,” in Mechanisms of primary energy transduction
in biology , M. Wikström, Ed. Royal Society of Chemistry, 2017, pp. 25–59.'
ista: 'Sazanov LA. 2017.Structure of respiratory complex I: “Minimal” bacterial
and “de luxe” mammalian versions. In: Mechanisms of primary energy transduction
in biology . , 25–59.'
mla: 'Sazanov, Leonid A. “Structure of Respiratory Complex I: ‘Minimal’ Bacterial
and ‘de Luxe’ Mammalian Versions.” Mechanisms of Primary Energy Transduction
in Biology , edited by Mårten Wikström, Royal Society of Chemistry, 2017,
pp. 25–59, doi:10.1039/9781788010405-00025.'
short: L.A. Sazanov, in:, M. Wikström (Ed.), Mechanisms of Primary Energy Transduction
in Biology , Royal Society of Chemistry, 2017, pp. 25–59.
date_created: 2018-12-11T11:46:30Z
date_published: 2017-11-29T00:00:00Z
date_updated: 2021-01-12T07:56:59Z
day: '29'
department:
- _id: LeSa
doi: 10.1039/9781788010405-00025
editor:
- first_name: Mårten
full_name: Wikström, Mårten
last_name: Wikström
language:
- iso: eng
month: '11'
oa_version: None
page: 25 - 59
publication: 'Mechanisms of primary energy transduction in biology '
publication_identifier:
isbn:
- 978-1-78262-865-1
publication_status: published
publisher: Royal Society of Chemistry
publist_id: '7379'
quality_controlled: '1'
series_title: 'Mechanisms of Primary Energy Transduction in Biology '
status: public
title: 'Structure of respiratory complex I: “Minimal” bacterial and “de luxe” mammalian
versions'
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2017'
...
---
_id: '515'
abstract:
- lang: eng
text: 'The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the
inner mitochondrial membrane is composed of five large protein complexes, named
CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule
used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC
complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI
forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome),
as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC
III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures
of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the
assembly and function of the SCs. Here we review and compare these recent studies
and discuss how they have advanced our understanding of mitochondrial electron
transport.'
article_type: original
author:
- first_name: James A
full_name: Letts, James A
id: 322DA418-F248-11E8-B48F-1D18A9856A87
last_name: Letts
orcid: 0000-0002-9864-3586
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: 'Letts JA, Sazanov LA. Clarifying the supercomplex: The higher-order organization
of the mitochondrial electron transport chain. Nature Structural and Molecular
Biology. 2017;24(10):800-808. doi:10.1038/nsmb.3460'
apa: 'Letts, J. A., & Sazanov, L. A. (2017). Clarifying the supercomplex: The
higher-order organization of the mitochondrial electron transport chain. Nature
Structural and Molecular Biology. Nature Publishing Group. https://doi.org/10.1038/nsmb.3460'
chicago: 'Letts, James A, and Leonid A Sazanov. “Clarifying the Supercomplex: The
Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature
Structural and Molecular Biology. Nature Publishing Group, 2017. https://doi.org/10.1038/nsmb.3460.'
ieee: 'J. A. Letts and L. A. Sazanov, “Clarifying the supercomplex: The higher-order
organization of the mitochondrial electron transport chain,” Nature Structural
and Molecular Biology, vol. 24, no. 10. Nature Publishing Group, pp. 800–808,
2017.'
ista: 'Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: The higher-order
organization of the mitochondrial electron transport chain. Nature Structural
and Molecular Biology. 24(10), 800–808.'
mla: 'Letts, James A., and Leonid A. Sazanov. “Clarifying the Supercomplex: The
Higher-Order Organization of the Mitochondrial Electron Transport Chain.” Nature
Structural and Molecular Biology, vol. 24, no. 10, Nature Publishing Group,
2017, pp. 800–08, doi:10.1038/nsmb.3460.'
short: J.A. Letts, L.A. Sazanov, Nature Structural and Molecular Biology 24 (2017)
800–808.
date_created: 2018-12-11T11:46:54Z
date_published: 2017-10-05T00:00:00Z
date_updated: 2021-01-12T08:01:17Z
day: '05'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/nsmb.3460
ec_funded: 1
file:
- access_level: open_access
checksum: 9bc7e8c41b43636dd7566289e511f096
content_type: application/pdf
creator: lsazanov
date_created: 2019-11-07T12:51:07Z
date_updated: 2020-07-14T12:46:36Z
file_id: '6993'
file_name: 29893_2_merged_1501257589_red.pdf
file_size: 4118385
relation: main_file
file_date_updated: 2020-07-14T12:46:36Z
has_accepted_license: '1'
intvolume: ' 24'
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 800 - 808
project:
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '701309'
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(H2020)
publication: Nature Structural and Molecular Biology
publication_identifier:
issn:
- '15459993'
publication_status: published
publisher: Nature Publishing Group
publist_id: '7304'
quality_controlled: '1'
scopus_import: 1
status: public
title: 'Clarifying the supercomplex: The higher-order organization of the mitochondrial
electron transport chain'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 24
year: '2017'
...
---
_id: '1226'
abstract:
- lang: eng
text: Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes
to cellular energy production by transferring electrons from NADH to ubiquinone
coupled to proton translocation across the membrane. It is the largest protein
assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we
present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial
complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking
and mass-spectrometry mapping experiments. All 14 conserved core subunits and
31 mitochondria-specific supernumerary subunits are resolved within the L-shaped
molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur
clusters involved in electron transfer, and the membrane arm contains 78 transmembrane
helices, mostly contributed by antiporter-like subunits involved in proton translocation.
Supernumerary subunits form an interlinked, stabilizing shell around the conserved
core. Tightly bound lipids (including cardiolipins) further stabilize interactions
between the hydrophobic subunits. Subunits with possible regulatory roles contain
additional cofactors, NADPH and two phosphopantetheine molecules, which are shown
to be involved in inter-subunit interactions. We observe two different conformations
of the complex, which may be related to the conformationally driven coupling mechanism
and to the active-deactive transition of the enzyme. Our structure provides insight
into the mechanism, assembly, maturation and dysfunction of mitochondrial complex
I, and allows detailed molecular analysis of disease-causing mutations.
article_processing_charge: No
article_type: original
author:
- first_name: Karol
full_name: Fiedorczuk, Karol
id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
last_name: Fiedorczuk
- first_name: James A
full_name: Letts, James A
id: 322DA418-F248-11E8-B48F-1D18A9856A87
last_name: Letts
orcid: 0000-0002-9864-3586
- first_name: Gianluca
full_name: Degliesposti, Gianluca
last_name: Degliesposti
- first_name: Karol
full_name: Kaszuba, Karol
id: 3FDF9472-F248-11E8-B48F-1D18A9856A87
last_name: Kaszuba
- first_name: Mark
full_name: Skehel, Mark
last_name: Skehel
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. Atomic
structure of the entire mammalian mitochondrial complex i. Nature. 2016;538(7625):406-410.
doi:10.1038/nature19794
apa: Fiedorczuk, K., Letts, J. A., Degliesposti, G., Kaszuba, K., Skehel, M., &
Sazanov, L. A. (2016). Atomic structure of the entire mammalian mitochondrial
complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19794
chicago: Fiedorczuk, Karol, James A Letts, Gianluca Degliesposti, Karol Kaszuba,
Mark Skehel, and Leonid A Sazanov. “Atomic Structure of the Entire Mammalian Mitochondrial
Complex I.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature19794.
ieee: K. Fiedorczuk, J. A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, and L.
A. Sazanov, “Atomic structure of the entire mammalian mitochondrial complex i,”
Nature, vol. 538, no. 7625. Nature Publishing Group, pp. 406–410, 2016.
ista: Fiedorczuk K, Letts JA, Degliesposti G, Kaszuba K, Skehel M, Sazanov LA. 2016.
Atomic structure of the entire mammalian mitochondrial complex i. Nature. 538(7625),
406–410.
mla: Fiedorczuk, Karol, et al. “Atomic Structure of the Entire Mammalian Mitochondrial
Complex I.” Nature, vol. 538, no. 7625, Nature Publishing Group, 2016,
pp. 406–10, doi:10.1038/nature19794.
short: K. Fiedorczuk, J.A. Letts, G. Degliesposti, K. Kaszuba, M. Skehel, L.A. Sazanov,
Nature 538 (2016) 406–410.
date_created: 2018-12-11T11:50:49Z
date_published: 2016-10-20T00:00:00Z
date_updated: 2021-01-12T06:49:13Z
day: '20'
department:
- _id: LeSa
doi: 10.1038/nature19794
ec_funded: 1
external_id:
pmid:
- '27595392'
intvolume: ' 538'
issue: '7625'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164932/
month: '10'
oa: 1
oa_version: Submitted Version
page: 406 - 410
pmid: 1
project:
- _id: 2593EBD6-B435-11E9-9278-68D0E5697425
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(FEBS)
- _id: 2590DB08-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '701309'
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(H2020)
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '6108'
quality_controlled: '1'
scopus_import: 1
status: public
title: Atomic structure of the entire mammalian mitochondrial complex i
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 538
year: '2016'
...
---
_id: '1232'
abstract:
- lang: eng
text: Mitochondrial electron transport chain complexes are organized into supercomplexes
responsible for carrying out cellular respiration. Here we present three architectures
of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We
identify two distinct arrangements of supercomplex CICIII 2 CIV (the respirasome)
- a major 'tight' form and a minor 'loose' form (resolved at the resolution of
5.8 Å and 6.7 Å, respectively), which may represent different stages in supercomplex
assembly or disassembly. We have also determined an architecture of supercomplex
CICIII 2 at 7.8 Å resolution. All observed density can be attributed to the known
80 subunits of the individual complexes, including 132 transmembrane helices.
The individual complexes form tight interactions that vary between the architectures,
with complex IV subunit COX7a switching contact from complex III to complex I.
The arrangement of active sites within the supercomplex may help control reactive
oxygen species production. To our knowledge, these are the first complete architectures
of the dominant, physiologically relevant state of the electron transport chain.
acknowledgement: We thank the MRC LMB Cambridge for the use of the Titan Krios microscope.
Data processing was performed using the IST high-performance computer cluster. J.A.L.
holds a long-term fellowship from FEBS. K.F. is partially funded by a MRC UK PhD
fellowship.
author:
- first_name: James A
full_name: Letts, James A
id: 322DA418-F248-11E8-B48F-1D18A9856A87
last_name: Letts
orcid: 0000-0002-9864-3586
- first_name: Karol
full_name: Fiedorczuk, Karol
id: 5BFF67CE-02D1-11E9-B11A-A5A4D7DFFFD0
last_name: Fiedorczuk
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Letts JA, Fiedorczuk K, Sazanov LA. The architecture of respiratory supercomplexes.
Nature. 2016;537(7622):644-648. doi:10.1038/nature19774
apa: Letts, J. A., Fiedorczuk, K., & Sazanov, L. A. (2016). The architecture
of respiratory supercomplexes. Nature. Nature Publishing Group. https://doi.org/10.1038/nature19774
chicago: Letts, James A, Karol Fiedorczuk, and Leonid A Sazanov. “The Architecture
of Respiratory Supercomplexes.” Nature. Nature Publishing Group, 2016.
https://doi.org/10.1038/nature19774.
ieee: J. A. Letts, K. Fiedorczuk, and L. A. Sazanov, “The architecture of respiratory
supercomplexes,” Nature, vol. 537, no. 7622. Nature Publishing Group, pp.
644–648, 2016.
ista: Letts JA, Fiedorczuk K, Sazanov LA. 2016. The architecture of respiratory
supercomplexes. Nature. 537(7622), 644–648.
mla: Letts, James A., et al. “The Architecture of Respiratory Supercomplexes.” Nature,
vol. 537, no. 7622, Nature Publishing Group, 2016, pp. 644–48, doi:10.1038/nature19774.
short: J.A. Letts, K. Fiedorczuk, L.A. Sazanov, Nature 537 (2016) 644–648.
date_created: 2018-12-11T11:50:51Z
date_published: 2016-09-29T00:00:00Z
date_updated: 2021-01-12T06:49:16Z
day: '29'
department:
- _id: LeSa
doi: 10.1038/nature19774
intvolume: ' 537'
issue: '7622'
language:
- iso: eng
month: '09'
oa_version: None
page: 644 - 648
project:
- _id: 2593EBD6-B435-11E9-9278-68D0E5697425
name: Atomic-Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes
(FEBS)
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '6102'
quality_controlled: '1'
scopus_import: 1
status: public
title: The architecture of respiratory supercomplexes
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 537
year: '2016'
...
---
_id: '1276'
abstract:
- lang: eng
text: The cytochrome (cyt) bc 1 complex is an integral component of the respiratory
electron transfer chain sustaining the energy needs of organisms ranging from
humans to bacteria. Due to its ubiquitous role in the energy metabolism, both
the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied
vigorously. Here, this vast amount of data is reassessed after probing the substrate
reduction steps at the Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus
using atomistic molecular dynamics simulations. The simulations suggest that the
Lys251 side chain could rotate into the Q i-site to facilitate binding of half-protonated
semiquinone-a reaction intermediate that is potentially formed during substrate
reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252,
thus making direct proton transfer possible. In the neutral state, the lysine
side chain stays close to the conserved binding location of cardiolipin (CL).
This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions
as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching,
which represents a refinement to the previously described CL/K pathway, fine-tunes
the proton transfer process. Lastly, the simulation data was used to formulate
a mechanism for reducing the substrate at the Q i-site.
acknowledgement: We wish to thank CSC – IT Centre for Science (Espoo, Finland) for
computational resources. For financial support, we wish to thank the Academy of
Finland (TR, IV and PAP; Center of Excellence in Biomembrane Research (IV, TR)),
the Finnish Doctoral Programme in Computational Sciences (KK), the Sigrid Juselius
Foundation (IV), the Paulo Foundation (PAP), and the European Research Council (IV,
TR; Advanced Grant project CROWDED-PRO-LIPIDS). AO acknowledges The Wellcome Trust
International Senior Research Fellowship.
article_number: '33607'
author:
- first_name: Pekka
full_name: Postila, Pekka
last_name: Postila
- first_name: Karol
full_name: Kaszuba, Karol
id: 3FDF9472-F248-11E8-B48F-1D18A9856A87
last_name: Kaszuba
- first_name: Patryk
full_name: Kuleta, Patryk
last_name: Kuleta
- first_name: Ilpo
full_name: Vattulainen, Ilpo
last_name: Vattulainen
- first_name: Marcin
full_name: Sarewicz, Marcin
last_name: Sarewicz
- first_name: Artur
full_name: Osyczka, Artur
last_name: Osyczka
- first_name: Tomasz
full_name: Róg, Tomasz
last_name: Róg
citation:
ama: Postila P, Kaszuba K, Kuleta P, et al. Atomistic determinants of co-enzyme
Q reduction at the Qi-site of the cytochrome bc1 complex. Scientific Reports.
2016;6. doi:10.1038/srep33607
apa: Postila, P., Kaszuba, K., Kuleta, P., Vattulainen, I., Sarewicz, M., Osyczka,
A., & Róg, T. (2016). Atomistic determinants of co-enzyme Q reduction at the
Qi-site of the cytochrome bc1 complex. Scientific Reports. Nature Publishing
Group. https://doi.org/10.1038/srep33607
chicago: Postila, Pekka, Karol Kaszuba, Patryk Kuleta, Ilpo Vattulainen, Marcin
Sarewicz, Artur Osyczka, and Tomasz Róg. “Atomistic Determinants of Co-Enzyme
Q Reduction at the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports.
Nature Publishing Group, 2016. https://doi.org/10.1038/srep33607.
ieee: P. Postila et al., “Atomistic determinants of co-enzyme Q reduction
at the Qi-site of the cytochrome bc1 complex,” Scientific Reports, vol.
6. Nature Publishing Group, 2016.
ista: Postila P, Kaszuba K, Kuleta P, Vattulainen I, Sarewicz M, Osyczka A, Róg
T. 2016. Atomistic determinants of co-enzyme Q reduction at the Qi-site of the
cytochrome bc1 complex. Scientific Reports. 6, 33607.
mla: Postila, Pekka, et al. “Atomistic Determinants of Co-Enzyme Q Reduction at
the Qi-Site of the Cytochrome Bc1 Complex.” Scientific Reports, vol. 6,
33607, Nature Publishing Group, 2016, doi:10.1038/srep33607.
short: P. Postila, K. Kaszuba, P. Kuleta, I. Vattulainen, M. Sarewicz, A. Osyczka,
T. Róg, Scientific Reports 6 (2016).
date_created: 2018-12-11T11:51:05Z
date_published: 2016-09-26T00:00:00Z
date_updated: 2021-01-12T06:49:34Z
day: '26'
ddc:
- '576'
department:
- _id: LeSa
doi: 10.1038/srep33607
file:
- access_level: open_access
checksum: 07c591c1250ebef266333cbc3228b4dd
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:17:09Z
date_updated: 2020-07-14T12:44:42Z
file_id: '5261'
file_name: IST-2016-691-v1+1_srep33607.pdf
file_size: 1960563
relation: main_file
file_date_updated: 2020-07-14T12:44:42Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Scientific Reports
publication_status: published
publisher: Nature Publishing Group
publist_id: '6040'
pubrep_id: '691'
quality_controlled: '1'
scopus_import: 1
status: public
title: Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome
bc1 complex
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2016'
...