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| Title | A universal coupling mechanism of respiratory complex I. |
|---|---|
| Journal, issue, pages | Nature, Vol. 609, Issue 7928, Page 808-814, Year 2022 |
| Publish date | Sep 14, 2022 |
 Authors | Vladyslav Kravchuk / Olga Petrova / Domen Kampjut / Anna Wojciechowska-Bason / Zara Breese / Leonid Sazanov /    |
| 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 ...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. |
 External links | Nature / PubMed:36104567 |
| Methods | EM (single particle) |
| Resolution | 2.15 - 4.0 Å |
| Structure data | EMDB-13214, PDB-7p61: EMDB-13215, PDB-7p62: EMDB-13216, PDB-7p63: EMDB-13217, PDB-7p64: EMDB-13222, PDB-7p69: EMDB-13235, PDB-7p7c: EMDB-13236, PDB-7p7e: EMDB-13237, PDB-7p7j: EMDB-13238, PDB-7p7k: EMDB-13239, PDB-7p7l: EMDB-13240, PDB-7p7m: EMDB-14535, PDB-7z7r: EMDB-14536, PDB-7z7s: EMDB-14537, PDB-7z7t: EMDB-14538, PDB-7z7v: EMDB-14540, PDB-7z80: EMDB-14541, PDB-7z83: EMDB-14542, PDB-7z84: EMDB-14620, PDB-7zc5: EMDB-14632, PDB-7zci: EMDB-14637, PDB-7zd6: EMDB-14648, PDB-7zdh: EMDB-14651, PDB-7zdj: EMDB-14658, PDB-7zdm: EMDB-14664, PDB-7zdp: EMDB-14688, PDB-7zeb:  EMDB-14815: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open-ready state, Entire consensus map  EMDB-14816: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open-ready state, PA focused map  EMDB-14817: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open-ready state, MD focused map  EMDB-14818: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Resting state, PA focused map  EMDB-14819: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Resting state, MD focused map  EMDB-14820: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Resting state, Entire consensus map  EMDB-14821: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Closed state, Entire consensus map  EMDB-14822: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Closed state, PA focused map  EMDB-14823: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Closed state, MD focused map  EMDB-14824: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open state, Entire consensus map  EMDB-14825: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open state, MD focused map  EMDB-14826: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open state, PA focused map  EMDB-14827: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open-ready state, Entire consensus map  EMDB-14828: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open-ready state, PA focused map  EMDB-14829: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Open-ready state, MD focused map  EMDB-14830: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Resting state, PA focused map  EMDB-14831: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Resting state, MD focused map  EMDB-14832: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open state, Entire consensus map  EMDB-14833: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open state, PA focused map  EMDB-14834: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Open state, MD focused map  EMDB-14835: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Closed state, Entire consensus map  EMDB-14836: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Closed state, PA focused map  EMDB-14837: Complex I from E. coli, LMNG-purified, under Turnover at pH 6, Closed state, MD focused map  EMDB-14838: Complex I from E. coli, LMNG-purified, Apo, Open-ready state, Entire consensus map  EMDB-14839: Complex I from E. coli, LMNG-purified, Apo, Open-ready state, NuoFEG focused map  EMDB-14840: Complex I from E. coli, LMNG-purified, Apo, Open-ready state, Interface focused map  EMDB-14841: Complex I from E. coli, LMNG-purified, Apo, Open-ready state, Antiporters focused map  EMDB-15064: Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 8, Resting state, Entire consensus map  EMDB-15068: Peripheral arm of Complex I from Ovis aries at pH7.4, Open state  EMDB-15069: Membrane domain of Complex I from Ovis aries at pH7.4, Open state  EMDB-15071: Consensus map of Complex I from Ovis aries at pH7.4, Open state  EMDB-15074: Membrane domain of Complex I from Ovis aries at pH7.4, Closed state  EMDB-15075: Consensus map of Complex I from Ovis aries at pH7.4, Closed state  EMDB-15077: Peripheral arm of Complex I from Ovis aries at pH7.4, Closed state  EMDB-15078: Peripheral arm of Complex I from Ovis aries at pH5.5, Open state  EMDB-15079: Membrane domain of Complex I from Ovis aries at pH5.5, Open state  EMDB-15080: Consensus map of Complex I from Ovis aries at pH5.5, Open state  EMDB-15081: Membrane domain of Complex I from Ovis aries at pH5.5, Closed state  EMDB-15082: Consensus map of Complex I from Ovis aries at pH5.5, Closed state  EMDB-15083: Peripheral arm of Complex I from Ovis aries at pH5.5, Closed state  EMDB-15094: Peripheral arm of Complex I from Ovis aries at pH9, Open state  EMDB-15095: Membrane domain of Complex I from Ovis aries at pH9, Open state  EMDB-15096: Consensus map of Complex I from Ovis aries at pH9, Open state  EMDB-15097: Peripheral arm of Complex I from Ovis aries at pH9, Closed state  EMDB-15098: Membrane domain of Complex I from Ovis aries at pH9, Closed state  EMDB-15099: Consensus map of Complex I from Ovis aries at pH9, Closed state |
| Chemicals |  ChemComp-SF4:  ChemComp-FMN:  ChemComp-NAI:  ChemComp-FES:  ChemComp-CA:  ChemComp-3PE:  ChemComp-UQ8:  ChemComp-DCQ:  ChemComp-LFA:  ChemComp-HOH:  ChemComp-HQH:  ChemComp-C14:  ChemComp-PC1:  ChemComp-ZMP:  ChemComp-AMP:  ChemComp-MYR:  ChemComp-K:  ChemComp-ZN:  ChemComp-NDP: |
| Source |
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 Keywords |  PROTON TRANSPORT / Complex I / NADH / Quinone / MEMBRANE PROTEIN / respiration / proton pump / mitochondria / iron-sulphur cluster / oxidoreductase |
