4HE8

Crystal structure of the membrane domain of respiratory complex I from Thermus thermophilus

Summary for 4HE8

• Entry DOI: 10.2210/pdb4he8/pdb
• Related: 4HEA
• Descriptor: NADH-quinone oxidoreductase subunit 7, NADH-quinone oxidoreductase subunit 10, NADH-quinone oxidoreductase subunit 11, ... (8 entities in total)
• Functional Keywords: nadh-quinone oxidoreductase, complex i, oxidoreductase, proton pump, membrane protein, nadh, menaquinone, cytoplasmic membrane
• Biological source: Thermus thermophilus; More
• Cellular location: Cell inner membrane; Multi-pass membrane protein: Q56217 Q56225 Q56226 Q56227 Q56228 Q56229 Q60019
• Total number of polymer chains: 14
• Total formula weight: 485298.83

Authors

Baradaran, R.,Berrisford, J.M.,Minhas, G.S.,Sazanov, L.A. (deposition date: 2012-10-03, release date: 2013-02-13, Last modification date: 2023-09-20)

Primary citation

Baradaran, R.,Berrisford, J.M.,Minhas, G.S.,Sazanov, L.A.
Crystal structure of the entire respiratory complex I.
Nature, 494:443-448, 2013

PubMed 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.

PubMed: 23417064
DOI: 10.1038/nature11871

Experimental method

X-RAY DIFFRACTION (3.3 Å)