6ZR2

Cryo-EM structure of respiratory complex I in the active state from Mus musculus at 3.1 A

6ZR2 の概要

• エントリーDOI: 10.2210/pdb6zr2/pdb
• 関連するPDBエントリー: 6ZTQ
• EMDBエントリー: 11377 11424 11425
• 分子名称: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 6, NADH-ubiquinone oxidoreductase chain 4L, ... (54 entities in total)
• 機能のキーワード: nadh, ubiquinone, complex i, oxidoreductase
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 45
• 化学式量合計: 1072324.86

構造登録者

Bridges, H.R.,Blaza, J.N.,Agip, A.N.A.,Hirst, J. (登録日: 2020-07-10, 公開日: 2020-10-21, 最終更新日: 2025-04-09)

主引用文献

Bridges, H.R.,Fedor, J.G.,Blaza, J.N.,Di Luca, A.,Jussupow, A.,Jarman, O.D.,Wright, J.J.,Agip, A.A.,Gamiz-Hernandez, A.P.,Roessler, M.M.,Kaila, V.R.I.,Hirst, J.
Structure of inhibitor-bound mammalian complex I.
Nat Commun, 11:5261-5261, 2020

PubMed Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I.

PubMed: 33067417
DOI: 10.1038/s41467-020-18950-3

実験手法

ELECTRON MICROSCOPY (3.1 Å)