8CA5

Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 3).

8CA5 の概要

• エントリーDOI: 10.2210/pdb8ca5/pdb
• 関連するPDBエントリー: 8C2S 8CA1 8CA2 8CA4
• EMDBエントリー: 16518
• 分子名称: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial, NADH-ubiquinone oxidoreductase chain 6, ... (53 entities in total)
• 機能のキーワード: nadh ubiquinone oxidoreductase, complex i, oxidoreductase
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 43
• 化学式量合計: 1039115.22

構造登録者

Yin, Z.,Bridges, H.R.,Agip, A.N.A.,Hirst, J. (登録日: 2023-01-24, 公開日: 2023-12-20, 最終更新日: 2024-10-16)

主引用文献

Yin, Z.,Agip, A.A.,Bridges, H.R.,Hirst, J.
Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 -/- mouse.
Embo J., 43:225-249, 2024

PubMed Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4 mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4 mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4 mouse model and complex I-linked mitochondrial disease.

PubMed: 38177503
DOI: 10.1038/s44318-023-00001-4

実験手法

ELECTRON MICROSCOPY (3.9 Å)