---
_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. <i>Nature Structural and Molecular Biology</i>. 2020;27(11):1077-1085.
    doi:<a href="https://doi.org/10.1038/s41594-020-0503-8">10.1038/s41594-020-0503-8</a>
  apa: Pinke, G., Zhou, L., &#38; Sazanov, L. A. (2020). Cryo-EM structure of the
    entire mammalian F-type ATP synthase. <i>Nature Structural and Molecular Biology</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41594-020-0503-8">https://doi.org/10.1038/s41594-020-0503-8</a>
  chicago: Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of
    the Entire Mammalian F-Type ATP Synthase.” <i>Nature Structural and Molecular
    Biology</i>. Springer Nature, 2020. <a href="https://doi.org/10.1038/s41594-020-0503-8">https://doi.org/10.1038/s41594-020-0503-8</a>.
  ieee: G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian
    F-type ATP synthase,” <i>Nature Structural and Molecular Biology</i>, 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.” <i>Nature Structural and Molecular Biology</i>, vol. 27, no. 11, Springer
    Nature, 2020, pp. 1077–85, doi:<a href="https://doi.org/10.1038/s41594-020-0503-8">10.1038/s41594-020-0503-8</a>.
  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: '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. <i>Nature Structural and Molecular
    Biology</i>. 2017;24(10):800-808. doi:<a href="https://doi.org/10.1038/nsmb.3460">10.1038/nsmb.3460</a>'
  apa: 'Letts, J. A., &#38; Sazanov, L. A. (2017). Clarifying the supercomplex: The
    higher-order organization of the mitochondrial electron transport chain. <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nsmb.3460">https://doi.org/10.1038/nsmb.3460</a>'
  chicago: 'Letts, James A, and Leonid A Sazanov. “Clarifying the Supercomplex: The
    Higher-Order Organization of the Mitochondrial Electron Transport Chain.” <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/nsmb.3460">https://doi.org/10.1038/nsmb.3460</a>.'
  ieee: 'J. A. Letts and L. A. Sazanov, “Clarifying the supercomplex: The higher-order
    organization of the mitochondrial electron transport chain,” <i>Nature Structural
    and Molecular Biology</i>, 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.” <i>Nature
    Structural and Molecular Biology</i>, vol. 24, no. 10, Nature Publishing Group,
    2017, pp. 800–08, doi:<a href="https://doi.org/10.1038/nsmb.3460">10.1038/nsmb.3460</a>.'
  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: '603'
abstract:
- lang: eng
  text: During transcription, RNA polymerase II (Pol II) associates with the conserved
    elongation factor DSIF. DSIF renders the elongation complex stable and functions
    during Pol II pausing and RNA processing. We combined cryo-EM and X-ray crystallography
    to determine the structure of the mammalian Pol II-DSIF elongation complex at
    a nominal resolution of 3.4. Human DSIF has a modular structure with two domains
    forming a DNA clamp, two domains forming an RNA clamp, and one domain buttressing
    the RNA clamp. The clamps maintain the transcription bubble, position upstream
    DNA, and retain the RNA transcript in the exit tunnel. The mobile C-terminal region
    of DSIF is located near exiting RNA, where it can recruit factors for RNA processing.
    The structure provides insight into the roles of DSIF during mRNA synthesis.
article_processing_charge: No
author:
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
- first_name: Jürgen
  full_name: Plitzko, Jürgen
  last_name: Plitzko
- first_name: Patrick
  full_name: Cramer, Patrick
  last_name: Cramer
citation:
  ama: Bernecky C, Plitzko J, Cramer P. Structure of a transcribing RNA polymerase
    II-DSIF complex reveals a multidentate DNA-RNA clamp. <i>Nature Structural and
    Molecular Biology</i>. 2017;24(10):809-815. doi:<a href="https://doi.org/10.1038/nsmb.3465">10.1038/nsmb.3465</a>
  apa: Bernecky, C., Plitzko, J., &#38; Cramer, P. (2017). Structure of a transcribing
    RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp. <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nsmb.3465">https://doi.org/10.1038/nsmb.3465</a>
  chicago: Bernecky, Carrie, Jürgen Plitzko, and Patrick Cramer. “Structure of a Transcribing
    RNA Polymerase II-DSIF Complex Reveals a Multidentate DNA-RNA Clamp.” <i>Nature
    Structural and Molecular Biology</i>. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/nsmb.3465">https://doi.org/10.1038/nsmb.3465</a>.
  ieee: C. Bernecky, J. Plitzko, and P. Cramer, “Structure of a transcribing RNA polymerase
    II-DSIF complex reveals a multidentate DNA-RNA clamp,” <i>Nature Structural and
    Molecular Biology</i>, vol. 24, no. 10. Nature Publishing Group, pp. 809–815,
    2017.
  ista: Bernecky C, Plitzko J, Cramer P. 2017. Structure of a transcribing RNA polymerase
    II-DSIF complex reveals a multidentate DNA-RNA clamp. Nature Structural and Molecular
    Biology. 24(10), 809–815.
  mla: Bernecky, Carrie, et al. “Structure of a Transcribing RNA Polymerase II-DSIF
    Complex Reveals a Multidentate DNA-RNA Clamp.” <i>Nature Structural and Molecular
    Biology</i>, vol. 24, no. 10, Nature Publishing Group, 2017, pp. 809–15, doi:<a
    href="https://doi.org/10.1038/nsmb.3465">10.1038/nsmb.3465</a>.
  short: C. Bernecky, J. Plitzko, P. Cramer, Nature Structural and Molecular Biology
    24 (2017) 809–815.
date_created: 2018-12-11T11:47:26Z
date_published: 2017-10-05T00:00:00Z
date_updated: 2021-01-12T08:05:47Z
day: '05'
doi: 10.1038/nsmb.3465
extern: '1'
intvolume: '        24'
issue: '10'
language:
- iso: eng
month: '10'
oa_version: None
page: 809 - 815
publication: Nature Structural and Molecular Biology
publication_identifier:
  issn:
  - '15459993'
publication_status: published
publisher: Nature Publishing Group
publist_id: '7202'
quality_controlled: '1'
status: public
title: Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate
  DNA-RNA clamp
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 24
year: '2017'
...