7P7C

Complex I from E. coli, DDM/LMNG-purified, Apo, Open state

7P7C の概要

• エントリーDOI: 10.2210/pdb7p7c/pdb
• EMDBエントリー: 13214 13215 13216 13217 13222 13235 13236 13237 13238 13239 13240
• 分子名称: NADH-quinone oxidoreductase subunit F, NADH dehydrogenase I subunit M, NADH-quinone oxidoreductase subunit N, ... (21 entities in total)
• 機能のキーワード: complex i, nadh, quinone, proton transport
• 由来する生物種: Escherichia coli BL21(DE3); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 548236.57

構造登録者

Kravchuk, V.,Kampjut, D.,Sazanov, L. (登録日: 2021-07-19, 公開日: 2022-09-21, 最終更新日: 2024-07-17)

主引用文献

Kravchuk, V.,Petrova, O.,Kampjut, D.,Wojciechowska-Bason, A.,Breese, Z.,Sazanov, L.
A universal coupling mechanism of respiratory complex I.
Nature, 609:808-814, 2022

PubMed Abstract: Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a 'domino effect' series of proton transfers and electrostatic interactions: the forward wave ('dominoes stacking') primes the pump, and the reverse wave ('dominoes falling') results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes.

PubMed: 36104567
DOI: 10.1038/s41586-022-05199-7

実験手法

ELECTRON MICROSCOPY (2.4 Å)