7p63
Complex I from E. coli, DDM/LMNG-purified, under Turnover at pH 6, Closed state
Structural highlights
FunctionNUOF_ECOLI NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be ubiquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient. Publication Abstract from PubMedComplex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria(1). Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane(2), 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(3), 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. A universal coupling mechanism of respiratory complex I.,Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov L Nature. 2022 Sep;609(7928):808-814. doi: 10.1038/s41586-022-05199-7. Epub 2022 , Sep 14. PMID:36104567[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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