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-Structure paper
タイトル | Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I. |
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ジャーナル・号・ページ | Science, Vol. 384, Issue 6701, Page 1247-1253, Year 2024 |
掲載日 | 2024年6月14日 |
著者 | Daniel N Grba / John J Wright / Zhan Yin / William Fisher / Judy Hirst / |
PubMed 要旨 | Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and ...Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and cellular damage. Ischemic conditions switch complex I from rapid, reversible catalysis into a dormant state that protects upon reoxygenation, but the molecular basis for the switch is unknown. We combined precise biochemical definition of complex I catalysis with high-resolution cryo-electron microscopy structures in the phospholipid bilayer of coupled vesicles to reveal the mechanism of the transition into the dormant state, modulated by membrane interactions. By implementing a versatile membrane system to unite structure and function, attributing catalytic and regulatory properties to specific structural states, we define how a conformational switch in complex I controls its physiological roles. |
リンク | Science / PubMed:38870289 |
手法 | EM (単粒子) |
解像度 | 2.5 - 3.8 Å |
構造データ | EMDB-18051, PDB-8q0a: EMDB-18052, PDB-8q0f: EMDB-18054: Inward-facing, slack proteoliposome complex I at 3.1 A. Initially purified in DDM. EMDB-18055, PDB-8q0m: EMDB-18057, PDB-8q0o: EMDB-18059: Outward-facing, slack proteoliposome complex I at 3.1 A. Initially purified in DDM. EMDB-18066, PDB-8q1p: EMDB-18067, PDB-8q1u: EMDB-18068, PDB-8q1y: EMDB-18069, PDB-8q25: EMDB-18138, PDB-8q45: EMDB-18139, PDB-8q46: EMDB-18140, PDB-8q47: EMDB-18141, PDB-8q48: EMDB-18142, PDB-8q49: EMDB-18143, PDB-8q4a: |
化合物 | ChemComp-3PE: ChemComp-PC1: ChemComp-PLC: ChemComp-SF4: ChemComp-FES: ChemComp-FMN: ChemComp-K: ChemComp-CDL: ChemComp-ZN: ChemComp-MG: ChemComp-DGT: ChemComp-NDP: ChemComp-EHZ: ChemComp-CHD: ChemComp-MYR: ChemComp-HOH: ChemComp-FVH: |
由来 |
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キーワード | MEMBRANE PROTEIN / Complex I / Oxidoreductase / Proteoliposomes / Membrane-bound / metabolism |