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Crystal structure of the entire respiratory complex I

Complex I is the first and largest enzyme of the respiratory chain, playing a central role in cellular energy production by coupling electron transfer between NADH and ubiquinone to proton translocation. It is implicated in many common human neurodegenerative diseases. Here we report the first cryst...

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Autores principales: Baradaran, Rozbeh, Berrisford, John M., Minhas, Gurdeep S., Sazanov, Leonid A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672946/
https://www.ncbi.nlm.nih.gov/pubmed/23417064
http://dx.doi.org/10.1038/nature11871
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author Baradaran, Rozbeh
Berrisford, John M.
Minhas, Gurdeep S.
Sazanov, Leonid A.
author_facet Baradaran, Rozbeh
Berrisford, John M.
Minhas, Gurdeep S.
Sazanov, Leonid A.
author_sort Baradaran, Rozbeh
collection PubMed
description Complex I is the first and largest enzyme of the respiratory chain, playing a central role in cellular energy production by coupling electron transfer between NADH and ubiquinone to proton translocation. It is implicated in many common human neurodegenerative diseases. Here we report the first crystal structure of the entire, intact complex I (from T. thermophilus) at 3.3 Å resolution. The structure of the 536 kDa complex comprises 16 different subunits with 64 transmembrane helices and 9 Fe-S clusters. The core fold of subunit Nqo8 (NuoH/ND1) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, thus completing the fourth proton translocation pathway, in addition to the channels in three antiporter-like subunits. The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near cluster N2. Strikingly, the chamber is linked to the fourth channel by a “funnel” of charged residues. The link continues over the entire membrane domain as a remarkable flexible central axis of charged and polar residues. It likely plays a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone reaction chamber allows the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle.
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spelling pubmed-36729462013-08-28 Crystal structure of the entire respiratory complex I Baradaran, Rozbeh Berrisford, John M. Minhas, Gurdeep S. Sazanov, Leonid A. Nature Article Complex I is the first and largest enzyme of the respiratory chain, playing a central role in cellular energy production by coupling electron transfer between NADH and ubiquinone to proton translocation. It is implicated in many common human neurodegenerative diseases. Here we report the first crystal structure of the entire, intact complex I (from T. thermophilus) at 3.3 Å resolution. The structure of the 536 kDa complex comprises 16 different subunits with 64 transmembrane helices and 9 Fe-S clusters. The core fold of subunit Nqo8 (NuoH/ND1) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, thus completing the fourth proton translocation pathway, in addition to the channels in three antiporter-like subunits. The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near cluster N2. Strikingly, the chamber is linked to the fourth channel by a “funnel” of charged residues. The link continues over the entire membrane domain as a remarkable flexible central axis of charged and polar residues. It likely plays a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone reaction chamber allows the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle. 2013-02-17 2013-02-28 /pmc/articles/PMC3672946/ /pubmed/23417064 http://dx.doi.org/10.1038/nature11871 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Baradaran, Rozbeh
Berrisford, John M.
Minhas, Gurdeep S.
Sazanov, Leonid A.
Crystal structure of the entire respiratory complex I
title Crystal structure of the entire respiratory complex I
title_full Crystal structure of the entire respiratory complex I
title_fullStr Crystal structure of the entire respiratory complex I
title_full_unstemmed Crystal structure of the entire respiratory complex I
title_short Crystal structure of the entire respiratory complex I
title_sort crystal structure of the entire respiratory complex i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672946/
https://www.ncbi.nlm.nih.gov/pubmed/23417064
http://dx.doi.org/10.1038/nature11871
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