title: Crystal structure of the entire respiratory complex I.
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.
authors: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors: Rozbeh
authors: R
authors: Baradaran
authors: John M
authors: JM
authors: Berrisford
authors: Gurdeep S
authors: GS
authors: Minhas
authors: Leonid A
authors: LA
authors: Sazanov
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D018892:Proton-Motive Force; D011522:Protons; D016963:Thermus thermophilus / Q000737:chemistry* / Q000166:cytology; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D021122:Protein Subunits; D011522:Protons; D009243:NAD; D014451:Ubiquinone; C004532:quinone; D042967:Electron Transport Complex I