---
_id: '10146'
abstract:
- lang: eng
text: The enzymes of the mitochondrial electron transport chain are key players
of cell metabolism. Despite being active when isolated, in vivo they associate
into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2
(refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in
mammals, but in contrast to CICIII2 and the respirasome, to date the only known
eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and
plants13, which have different organization. Here we present the first, to our
knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly
intermediates, in different conformations. We describe the assembly of CIII2CIV
from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion
of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while
its C terminus is integrated into CIV. Our structures (which include CICIII2 and
the respirasome) also confirm that SCAF1 is exclusively required for the assembly
of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2
is asymmetric due to the presence of only one copy of subunit 9, which straddles
both monomers and prevents the attachment of a second copy of SCAF1 to CIII2,
explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we
show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex
and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer
in the electron transport chain.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: ScienComp
acknowledgement: We thank the pre-clinical facility of the IST Austria and A. Venturino
for assistance with the animals; and V.-V. Hodirnau for assistance during the Titan
Krios data collection, performed at the IST Austria. The data processing was performed
at the IST high-performance computing cluster. This project has received funding
from the European Union’s Horizon 2020 research and innovation program under the
Marie Skłodowska-Curie grant agreement no. 754411.
article_processing_charge: No
article_type: original
author:
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
- 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: Vercellino I, Sazanov LA. Structure and assembly of the mammalian mitochondrial
supercomplex CIII2CIV. Nature. 2021;598(7880):364-367. doi:10.1038/s41586-021-03927-z
apa: Vercellino, I., & Sazanov, L. A. (2021). Structure and assembly of the
mammalian mitochondrial supercomplex CIII2CIV. Nature. Springer
Nature. https://doi.org/10.1038/s41586-021-03927-z
chicago: Vercellino, Irene, and Leonid A Sazanov. “Structure and Assembly of the
Mammalian Mitochondrial Supercomplex CIII2CIV.” Nature. Springer
Nature, 2021. https://doi.org/10.1038/s41586-021-03927-z.
ieee: I. Vercellino and L. A. Sazanov, “Structure and assembly of the mammalian
mitochondrial supercomplex CIII2CIV,” Nature, vol. 598, no.
7880. Springer Nature, pp. 364–367, 2021.
ista: Vercellino I, Sazanov LA. 2021. Structure and assembly of the mammalian mitochondrial
supercomplex CIII2CIV. Nature. 598(7880), 364–367.
mla: Vercellino, Irene, and Leonid A. Sazanov. “Structure and Assembly of the Mammalian
Mitochondrial Supercomplex CIII2CIV.” Nature, vol. 598, no.
7880, Springer Nature, 2021, pp. 364–67, doi:10.1038/s41586-021-03927-z.
short: I. Vercellino, L.A. Sazanov, Nature 598 (2021) 364–367.
date_created: 2021-10-17T22:01:17Z
date_published: 2021-10-14T00:00:00Z
date_updated: 2023-08-14T08:01:21Z
day: '14'
department:
- _id: LeSa
doi: 10.1038/s41586-021-03927-z
ec_funded: 1
external_id:
isi:
- '000704581600001'
pmid:
- '34616041'
intvolume: ' 598'
isi: 1
issue: '7880'
language:
- iso: eng
month: '10'
oa_version: None
page: 364-367
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
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 Webpage
relation: press_release
url: https://ist.ac.at/en/news/boosting-the-cells-power-house/
scopus_import: '1'
status: public
title: Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 598
year: '2021'
...
---
_id: '10310'
abstract:
- lang: eng
text: A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI)
from Thermosynechococcus elongatus was reported as the first atomic model of PSI
almost 20 years ago. However, the monomeric PSI structure has not yet been reported
despite long-standing interest in its structure and extensive spectroscopic characterization
of the loss of red chlorophylls upon monomerization. Here, we describe the structure
of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the
trimer structure gave detailed insights into monomerization-induced changes in
both the central trimerization domain and the peripheral regions of the complex.
Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls
adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization
of red chlorophylls and that lipids of the surrounding membrane present a major
source of thermal energy for uphill excitation energy transfer from red chlorophylls
to P700.
acknowledgement: We are grateful for additional support and valuable scientific input
for this project by Yuko Misumi, Jiannan Li, Hisako Kubota-Kawai, Takeshi Kawabata,
Mian Wu, Eiki Yamashita, Atsushi Nakagawa, Volker Hartmann, Melanie Völkel and Matthias
Rögner. Parts of this research were funded by the German Research Council (DFG)
within the framework of GRK 2341 (Microbial Substrate Conversion) to M.M.N., the
Platform Project for Supporting Drug Discovery and Life Science Research [Basis
for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from
AMED under grant number JP20am0101117 (K.N.), JP16K07266 to Atsunori Oshima and
C.G., a Grants-in-Aid for Scientific Research under grant number JP 25000013 (K.N.),
17H03647 (C.G.) and 16H06560 (G.K.) from MEXT-KAKENHI, the International Joint Research
Promotion Program from Osaka University to M.M.N., C.G. and G.K., and the Cyclic
Innovation for Clinical Empowerment (CiCLE) Grant Number JP17pc0101020 from AMED
to K.N. and G.K.
article_number: '304'
article_processing_charge: No
article_type: original
author:
- first_name: Mehmet Orkun
full_name: Çoruh, Mehmet Orkun
id: d25163e5-8d53-11eb-a251-e6dd8ea1b8ef
last_name: Çoruh
orcid: 0000-0002-3219-2022
- first_name: Anna
full_name: Frank, Anna
last_name: Frank
- first_name: Hideaki
full_name: Tanaka, Hideaki
last_name: Tanaka
- first_name: Akihiro
full_name: Kawamoto, Akihiro
last_name: Kawamoto
- first_name: Eithar
full_name: El-Mohsnawy, Eithar
last_name: El-Mohsnawy
- first_name: Takayuki
full_name: Kato, Takayuki
last_name: Kato
- first_name: Keiichi
full_name: Namba, Keiichi
last_name: Namba
- first_name: Christoph
full_name: Gerle, Christoph
last_name: Gerle
- first_name: Marc M.
full_name: Nowaczyk, Marc M.
last_name: Nowaczyk
- first_name: Genji
full_name: Kurisu, Genji
last_name: Kurisu
citation:
ama: Çoruh MO, Frank A, Tanaka H, et al. Cryo-EM structure of a functional monomeric
Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster.
Communications Biology. 2021;4(1). doi:10.1038/s42003-021-01808-9
apa: Çoruh, M. O., Frank, A., Tanaka, H., Kawamoto, A., El-Mohsnawy, E., Kato, T.,
… Kurisu, G. (2021). Cryo-EM structure of a functional monomeric Photosystem I
from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications
Biology. Springer . https://doi.org/10.1038/s42003-021-01808-9
chicago: Çoruh, Mehmet Orkun, Anna Frank, Hideaki Tanaka, Akihiro Kawamoto, Eithar
El-Mohsnawy, Takayuki Kato, Keiichi Namba, Christoph Gerle, Marc M. Nowaczyk,
and Genji Kurisu. “Cryo-EM Structure of a Functional Monomeric Photosystem I from
Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications
Biology. Springer , 2021. https://doi.org/10.1038/s42003-021-01808-9.
ieee: M. O. Çoruh et al., “Cryo-EM structure of a functional monomeric Photosystem
I from Thermosynechococcus elongatus reveals red chlorophyll cluster,” Communications
Biology, vol. 4, no. 1. Springer , 2021.
ista: Çoruh MO, Frank A, Tanaka H, Kawamoto A, El-Mohsnawy E, Kato T, Namba K, Gerle
C, Nowaczyk MM, Kurisu G. 2021. Cryo-EM structure of a functional monomeric Photosystem
I from Thermosynechococcus elongatus reveals red chlorophyll cluster. Communications
Biology. 4(1), 304.
mla: Çoruh, Mehmet Orkun, et al. “Cryo-EM Structure of a Functional Monomeric Photosystem
I from Thermosynechococcus Elongatus Reveals Red Chlorophyll Cluster.” Communications
Biology, vol. 4, no. 1, 304, Springer , 2021, doi:10.1038/s42003-021-01808-9.
short: M.O. Çoruh, A. Frank, H. Tanaka, A. Kawamoto, E. El-Mohsnawy, T. Kato, K.
Namba, C. Gerle, M.M. Nowaczyk, G. Kurisu, Communications Biology 4 (2021).
date_created: 2021-11-19T11:37:29Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2023-08-14T11:51:19Z
day: '08'
ddc:
- '570'
department:
- _id: LeSa
doi: 10.1038/s42003-021-01808-9
external_id:
isi:
- '000627440700001'
pmid:
- '33686186'
file:
- access_level: open_access
checksum: 8ffd39f2bba7152a2441802ff313bf0b
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-19T15:09:18Z
date_updated: 2021-11-19T15:09:18Z
file_id: '10318'
file_name: 2021_CommBio_Çoruh.pdf
file_size: 6030261
relation: main_file
success: 1
file_date_updated: 2021-11-19T15:09:18Z
has_accepted_license: '1'
intvolume: ' 4'
isi: 1
issue: '1'
keyword:
- general agricultural and biological Sciences
- general biochemistry
- genetics and molecular biology
- medicine (miscellaneous)
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
issn:
- 2399-3642
publication_status: published
publisher: 'Springer '
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus
elongatus reveals red chlorophyll cluster
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: 4
year: '2021'
...
---
_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: '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
license: https://creativecommons.org/licenses/by-nc/4.0/
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'
...