Crystal structure of the entire respiratory complex i Journal Article


Author(s): Baradaran, Rozbeh ; Berrisford, John M; Minhas, Gurdeep S; Sazanov, Leonid A
Article Title: Crystal structure of the entire respiratory complex i
Alternate Title: Nature
Affiliation
Abstract: Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 Å resolution. The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present 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 iron-sulphur cluster N2. Notably, the chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has 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 enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle.
Keywords: quinone derivative; antiporter; iron sulfur protein; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)
Journal Title: Nature
Volume: 494
Issue 7438
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2013-02-28
Start Page: 443
End Page: 448
Sponsor: This work was funded by the Medical Research Council.
DOI: 10.1038/nature11871
Open access: no