---
_id: '8318'
abstract:
- lang: eng
text: Complex I is the first and the largest enzyme of respiratory chains in bacteria
and mitochondria. The mechanism which couples spatially separated transfer of
electrons to proton translocation in complex I is not known. Here we report five
crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like
compounds. We also determined cryo-EM structures of major and minor native states
of the complex, differing in the position of the peripheral arm. Crystal structures
show that binding of quinone-like compounds (but not of NADH) leads to a related
global conformational change, accompanied by local re-arrangements propagating
from the quinone site to the nearest proton channel. Normal mode and molecular
dynamics analyses indicate that these are likely to represent the first steps
in the proton translocation mechanism. Our results suggest that quinone binding
and chemistry play a key role in the coupling mechanism of complex I.
acknowledgement: This work was funded by the Medical Research Council, UK and IST
Austria. We thank the European Synchrotron Radiation Facility and the Diamond Light
Source for provision of synchrotron radiation facilities. We are grateful to the
staff of beamlines ID29, ID23-2 (ESRF, Grenoble, France) and I03 (Diamond Light
Source, Didcot, UK) for assistance. Data processing was performed at the IST high-performance
computing cluster.
article_number: '4135'
article_processing_charge: No
article_type: original
author:
- first_name: Javier
full_name: Gutierrez-Fernandez, Javier
id: 3D9511BA-F248-11E8-B48F-1D18A9856A87
last_name: Gutierrez-Fernandez
- first_name: Karol
full_name: Kaszuba, Karol
id: 3FDF9472-F248-11E8-B48F-1D18A9856A87
last_name: Kaszuba
- first_name: Gurdeep S.
full_name: Minhas, Gurdeep S.
last_name: Minhas
- first_name: Rozbeh
full_name: Baradaran, Rozbeh
last_name: Baradaran
- first_name: Margherita
full_name: Tambalo, Margherita
id: 4187dfe4-ec23-11ea-ae46-f08ab378313a
last_name: Tambalo
- first_name: David T.
full_name: Gallagher, David T.
last_name: Gallagher
- 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: Gutierrez-Fernandez J, Kaszuba K, Minhas GS, et al. Key role of quinone in
the mechanism of respiratory complex I. Nature Communications. 2020;11(1).
doi:10.1038/s41467-020-17957-0
apa: Gutierrez-Fernandez, J., Kaszuba, K., Minhas, G. S., Baradaran, R., Tambalo,
M., Gallagher, D. T., & Sazanov, L. A. (2020). Key role of quinone in the
mechanism of respiratory complex I. Nature Communications. Springer Nature.
https://doi.org/10.1038/s41467-020-17957-0
chicago: Gutierrez-Fernandez, Javier, Karol Kaszuba, Gurdeep S. Minhas, Rozbeh Baradaran,
Margherita Tambalo, David T. Gallagher, and Leonid A Sazanov. “Key Role of Quinone
in the Mechanism of Respiratory Complex I.” Nature Communications. Springer
Nature, 2020. https://doi.org/10.1038/s41467-020-17957-0.
ieee: J. Gutierrez-Fernandez et al., “Key role of quinone in the mechanism
of respiratory complex I,” Nature Communications, vol. 11, no. 1. Springer
Nature, 2020.
ista: Gutierrez-Fernandez J, Kaszuba K, Minhas GS, Baradaran R, Tambalo M, Gallagher
DT, Sazanov LA. 2020. Key role of quinone in the mechanism of respiratory complex
I. Nature Communications. 11(1), 4135.
mla: Gutierrez-Fernandez, Javier, et al. “Key Role of Quinone in the Mechanism of
Respiratory Complex I.” Nature Communications, vol. 11, no. 1, 4135, Springer
Nature, 2020, doi:10.1038/s41467-020-17957-0.
short: J. Gutierrez-Fernandez, K. Kaszuba, G.S. Minhas, R. Baradaran, M. Tambalo,
D.T. Gallagher, L.A. Sazanov, Nature Communications 11 (2020).
date_created: 2020-08-30T22:01:10Z
date_published: 2020-08-18T00:00:00Z
date_updated: 2023-08-22T09:03:00Z
day: '18'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1038/s41467-020-17957-0
external_id:
isi:
- '000607072900001'
pmid:
- '32811817'
file:
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checksum: 52b96f41d7d0db9728064c08da00d030
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creator: cziletti
date_created: 2020-08-31T13:40:00Z
date_updated: 2020-08-31T13:40:00Z
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file_date_updated: 2020-08-31T13:40:00Z
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issue: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- '20411723'
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/mystery-of-giant-proton-pump-solved/
scopus_import: '1'
status: public
title: Key role of quinone in the mechanism of respiratory complex I
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: 11
year: '2020'
...
---
_id: '1186'
abstract:
- lang: eng
text: The human pathogen Streptococcus pneumoniae is decorated with a special class
of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine
(PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography,
NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies,
we provide structural information of choline-binding protein L (CbpL) and demonstrate
its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated
three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported
in this work for the very first time-, (ii) an unprecedented anchorage module
showing alternate disposition of canonical and non-canonical choline-binding sites
that allows vine-like binding of fully-PCho-substituted teichoic acids (with two
choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural
and infection assays indicate an important role of the whole multimodular protein
allowing both to locate CbpL at specific places on the cell wall and to interact
with host components in order to facilitate pneumococcal lung infection and transmigration
from nasopharynx to the lungs and blood. CbpL implication in both resistance against
killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein
as relevant among the pathogenic arsenal of the pneumococcus.
acknowledgement: We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann,
for technical assistance and Lothar Petruschka for in silico analysis (all Dept.
of Genetics, University of Greifswald). We are further grateful to the staff from
SLS synchrotron beamline for help in data collection. This work was supported by
grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish
Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P
to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD-2457 (Community of Madrid to
JAH and FG).
article_number: '38094'
author:
- first_name: Javier
full_name: Gutierrez-Fernandez, Javier
id: 3D9511BA-F248-11E8-B48F-1D18A9856A87
last_name: Gutierrez-Fernandez
- first_name: Malek
full_name: Saleh, Malek
last_name: Saleh
- first_name: Martín
full_name: Alcorlo, Martín
last_name: Alcorlo
- first_name: Alejandro
full_name: Gómez Mejóa, Alejandro
last_name: Gómez Mejóa
- first_name: David
full_name: Pantoja Uceda, David
last_name: Pantoja Uceda
- first_name: Miguel
full_name: Treviño, Miguel
last_name: Treviño
- first_name: Franziska
full_name: Vob, Franziska
last_name: Vob
- first_name: Mohammed
full_name: Abdullah, Mohammed
last_name: Abdullah
- first_name: Sergio
full_name: Galán Bartual, Sergio
last_name: Galán Bartual
- first_name: Jolien
full_name: Seinen, Jolien
last_name: Seinen
- first_name: Pedro
full_name: Sánchez Murcia, Pedro
last_name: Sánchez Murcia
- first_name: Federico
full_name: Gago, Federico
last_name: Gago
- first_name: Marta
full_name: Bruix, Marta
last_name: Bruix
- first_name: Sven
full_name: Hammerschmidt, Sven
last_name: Hammerschmidt
- first_name: Juan
full_name: Hermoso, Juan
last_name: Hermoso
citation:
ama: Gutierrez-Fernandez J, Saleh M, Alcorlo M, et al. Modular architecture and
unique teichoic acid recognition features of choline-binding protein L CbpL contributing
to pneumococcal pathogenesis. Scientific Reports. 2016;6. doi:10.1038/srep38094
apa: Gutierrez-Fernandez, J., Saleh, M., Alcorlo, M., Gómez Mejóa, A., Pantoja Uceda,
D., Treviño, M., … Hermoso, J. (2016). Modular architecture and unique teichoic
acid recognition features of choline-binding protein L CbpL contributing to pneumococcal
pathogenesis. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep38094
chicago: Gutierrez-Fernandez, Javier, Malek Saleh, Martín Alcorlo, Alejandro Gómez
Mejóa, David Pantoja Uceda, Miguel Treviño, Franziska Vob, et al. “Modular Architecture
and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL
Contributing to Pneumococcal Pathogenesis.” Scientific Reports. Nature
Publishing Group, 2016. https://doi.org/10.1038/srep38094.
ieee: J. Gutierrez-Fernandez et al., “Modular architecture and unique teichoic
acid recognition features of choline-binding protein L CbpL contributing to pneumococcal
pathogenesis,” Scientific Reports, vol. 6. Nature Publishing Group, 2016.
ista: Gutierrez-Fernandez J, Saleh M, Alcorlo M, Gómez Mejóa A, Pantoja Uceda D,
Treviño M, Vob F, Abdullah M, Galán Bartual S, Seinen J, Sánchez Murcia P, Gago
F, Bruix M, Hammerschmidt S, Hermoso J. 2016. Modular architecture and unique
teichoic acid recognition features of choline-binding protein L CbpL contributing
to pneumococcal pathogenesis. Scientific Reports. 6, 38094.
mla: Gutierrez-Fernandez, Javier, et al. “Modular Architecture and Unique Teichoic
Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal
Pathogenesis.” Scientific Reports, vol. 6, 38094, Nature Publishing Group,
2016, doi:10.1038/srep38094.
short: J. Gutierrez-Fernandez, M. Saleh, M. Alcorlo, A. Gómez Mejóa, D. Pantoja
Uceda, M. Treviño, F. Vob, M. Abdullah, S. Galán Bartual, J. Seinen, P. Sánchez
Murcia, F. Gago, M. Bruix, S. Hammerschmidt, J. Hermoso, Scientific Reports 6
(2016).
date_created: 2018-12-11T11:50:36Z
date_published: 2016-12-05T00:00:00Z
date_updated: 2021-01-12T06:48:56Z
day: '05'
ddc:
- '576'
- '610'
department:
- _id: LeSa
doi: 10.1038/srep38094
file:
- access_level: open_access
checksum: e007d78b483bc59bf5ab98e9d42a6ec1
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:18Z
date_updated: 2020-07-14T12:44:37Z
file_id: '4804'
file_name: IST-2017-735-v1+1_srep38094.pdf
file_size: 2716045
relation: main_file
file_date_updated: 2020-07-14T12:44:37Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: Scientific Reports
publication_status: published
publisher: Nature Publishing Group
publist_id: '6167'
pubrep_id: '735'
quality_controlled: '1'
scopus_import: 1
status: public
title: Modular architecture and unique teichoic acid recognition features of choline-binding
protein L CbpL contributing to pneumococcal pathogenesis
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'
...