---
_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: '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: '6507'
abstract:
- lang: eng
text: The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor
with important roles in dendritic cell maturation and activation of inflammatory
monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR
ectodomain is presented, both free and in complex with a consensus triple-helical
peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like
domain (D1 and D2). The THP binds near a predicted collagen-binding groove in
D1, but a more extensive interaction with D2 is facilitated by the unusually wide
D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed
mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in
D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI)
and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR
D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows
a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due
to an avidity effect. These data suggest a 2-stage model for the interaction of
OSCAR with a collagen fibril, with transient, low-affinity interactions initiated
by the membrane-distal D1, followed by firm adhesion to the primary binding site
in D2.
author:
- first_name: Long
full_name: Zhou, Long
id: 3E751364-F248-11E8-B48F-1D18A9856A87
last_name: Zhou
orcid: 0000-0002-1864-8951
- first_name: J. M.
full_name: Hinerman, J. M.
last_name: Hinerman
- first_name: M.
full_name: Blaszczyk, M.
last_name: Blaszczyk
- first_name: J. L. C.
full_name: Miller, J. L. C.
last_name: Miller
- first_name: D. G.
full_name: Conrady, D. G.
last_name: Conrady
- first_name: A. D.
full_name: Barrow, A. D.
last_name: Barrow
- first_name: D. Y.
full_name: Chirgadze, D. Y.
last_name: Chirgadze
- first_name: D.
full_name: Bihan, D.
last_name: Bihan
- first_name: R. W.
full_name: Farndale, R. W.
last_name: Farndale
- first_name: A. B.
full_name: Herr, A. B.
last_name: Herr
citation:
ama: Zhou L, Hinerman JM, Blaszczyk M, et al. Structural basis for collagen recognition
by the immune receptor OSCAR. Blood. 2015;127(5):529-537. doi:10.1182/blood-2015-08-667055
apa: Zhou, L., Hinerman, J. M., Blaszczyk, M., Miller, J. L. C., Conrady, D. G.,
Barrow, A. D., … Herr, A. B. (2015). Structural basis for collagen recognition
by the immune receptor OSCAR. Blood. American Society of Hematology. https://doi.org/10.1182/blood-2015-08-667055
chicago: Zhou, Long, J. M. Hinerman, M. Blaszczyk, J. L. C. Miller, D. G. Conrady,
A. D. Barrow, D. Y. Chirgadze, D. Bihan, R. W. Farndale, and A. B. Herr. “Structural
Basis for Collagen Recognition by the Immune Receptor OSCAR.” Blood. American
Society of Hematology, 2015. https://doi.org/10.1182/blood-2015-08-667055.
ieee: L. Zhou et al., “Structural basis for collagen recognition by the immune
receptor OSCAR,” Blood, vol. 127, no. 5. American Society of Hematology,
pp. 529–537, 2015.
ista: Zhou L, Hinerman JM, Blaszczyk M, Miller JLC, Conrady DG, Barrow AD, Chirgadze
DY, Bihan D, Farndale RW, Herr AB. 2015. Structural basis for collagen recognition
by the immune receptor OSCAR. Blood. 127(5), 529–537.
mla: Zhou, Long, et al. “Structural Basis for Collagen Recognition by the Immune
Receptor OSCAR.” Blood, vol. 127, no. 5, American Society of Hematology,
2015, pp. 529–37, doi:10.1182/blood-2015-08-667055.
short: L. Zhou, J.M. Hinerman, M. Blaszczyk, J.L.C. Miller, D.G. Conrady, A.D. Barrow,
D.Y. Chirgadze, D. Bihan, R.W. Farndale, A.B. Herr, Blood 127 (2015) 529–537.
date_created: 2019-05-31T09:38:50Z
date_published: 2015-11-02T00:00:00Z
date_updated: 2021-01-12T08:07:47Z
day: '02'
doi: 10.1182/blood-2015-08-667055
extern: '1'
external_id:
pmid:
- '26552697'
intvolume: ' 127'
issue: '5'
language:
- iso: eng
month: '11'
oa_version: None
page: 529-537
pmid: 1
publication: Blood
publication_identifier:
issn:
- 0006-4971
- 1528-0020
publication_status: published
publisher: American Society of Hematology
quality_controlled: '1'
status: public
title: Structural basis for collagen recognition by the immune receptor OSCAR
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 127
year: '2015'
...