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-Structure paper
タイトル | Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 31, Page eadi1359, Year 2023 |
掲載日 | 2023年8月2日 |
著者 | Daniel N Grba / Injae Chung / Hannah R Bridges / Ahmed-Noor A Agip / Judy Hirst / |
PubMed 要旨 | Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the ...Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them. |
リンク | Sci Adv / PubMed:37531432 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.39 - 2.84 Å |
構造データ | EMDB-16962, PDB-8olt: EMDB-16965, PDB-8om1: |
化合物 | ChemComp-LMT: ChemComp-PC1: ChemComp-SF4: ChemComp-HQH: ChemComp-FES: ChemComp-FMN: ChemComp-NA: ChemComp-CDL: ChemComp-3PE: ChemComp-MG: ChemComp-GTP: ChemComp-NDP: ChemComp-ZN: ChemComp-EHZ: ChemComp-MYR: ChemComp-HOH: ChemComp-DGT: |
由来 |
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キーワード | OXIDOREDUCTASE / Mitochondrial complex I / Respiratory complex I / NADH:ubiquinone oxidoreductase |