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Title | Conformational coupling of redox-driven Na-translocation in Vibrio cholerae NADH:quinone oxidoreductase. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 11, Page 1686-1694, Year 2023 |
Publish date | Sep 14, 2023 |
Authors | Jann-Louis Hau / Susann Kaltwasser / Valentin Muras / Marco S Casutt / Georg Vohl / Björn Claußen / Wojtek Steffen / Alexander Leitner / Eckhard Bill / George E Cutsail / Serena DeBeer / Janet Vonck / Julia Steuber / Günter Fritz / |
PubMed Abstract | In the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH: ...In the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH:quinone oxidoreductase (Na-NQR) generates a sodium gradient by a so far unknown mechanism. Here we show that ion pumping in Na-NQR is driven by large conformational changes coupling electron transfer to ion translocation. We have determined a series of cryo-EM and X-ray structures of the Na-NQR that represent snapshots of the catalytic cycle. The six subunits NqrA, B, C, D, E, and F of Na-NQR harbor a unique set of cofactors that shuttle the electrons from NADH twice across the membrane to quinone. The redox state of a unique intramembranous [2Fe-2S] cluster orchestrates the movements of subunit NqrC, which acts as an electron transfer switch. We propose that this switching movement controls the release of Na from a binding site localized in subunit NqrB. |
External links | Nat Struct Mol Biol / PubMed:37710014 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.5 - 3.5 Å |
Structure data | EMDB-15088, PDB-8a1t: EMDB-15089, PDB-8a1u: EMDB-15090, PDB-8a1v: EMDB-15091, PDB-8a1w: EMDB-15092, PDB-8a1x: EMDB-15093, PDB-8a1y: PDB-8acw: PDB-8acy: PDB-8ad3: PDB-8ad4: PDB-8ad5: |
Chemicals | ChemComp-FMN: ChemComp-RBF: ChemComp-LMT: ChemComp-3PE: ChemComp-NA: ChemComp-K: ChemComp-FES: ChemComp-FAD: ChemComp-UQ2: ChemComp-NAI: ChemComp-HOH: ChemComp-UQ1: ChemComp-HQO: ChemComp-LYS: ChemComp-MG: ChemComp-SO4: |
Source |
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Keywords | MEMBRANE PROTEIN / quinone / NADH / sodium pump / inhibitor / respiratory complex / NADH ubiquinone oxido reducatase / Na+ pump / FLAVOPROTEIN / FAD / Na+-NQR |