7AK5

Cryo-EM structure of respiratory complex I in the deactive state from Mus musculus at 3.2 A

7AK5 の概要

• エントリーDOI: 10.2210/pdb7ak5/pdb
• EMDBエントリー: 11810
• 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: deactive 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: 1063250.64

構造登録者

Yin, Z.,Bridges, H.R.,Grba, D.,Hirst, J. (登録日: 2020-09-29, 公開日: 2021-02-03, 最終更新日: 2025-04-09)

主引用文献

Yin, Z.,Burger, N.,Kula-Alwar, D.,Aksentijevic, D.,Bridges, H.R.,Prag, H.A.,Grba, D.N.,Viscomi, C.,James, A.M.,Mottahedin, A.,Krieg, T.,Murphy, M.P.,Hirst, J.
Structural basis for a complex I mutation that blocks pathological ROS production.
Nat Commun, 12:707-707, 2021

PubMed Abstract: Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.

PubMed: 33514727
DOI: 10.1038/s41467-021-20942-w

実験手法

ELECTRON MICROSCOPY (3.17 Å)