8Q4A

Outward-facing, open1 proteoliposome complex I at 2.6 A. Initially purified in LMNG.

Summary for 8Q4A

• Entry DOI: 10.2210/pdb8q4a/pdb
• Related: 8Q45 8Q46 8Q47 8Q48 8Q49
• EMDB information: 18138 18139 18140 18141 18142 18143
• Descriptor: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 6, NADH-ubiquinone oxidoreductase chain 4L, ... (61 entities in total)
• Functional Keywords: complex i, oxidoreductase, proteoliposomes, membrane-bound, metabolism, membrane protein
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 45
• Total formula weight: 1104242.89

Authors

Grba, D.N.,Hirst, J. (deposition date: 2023-08-05, release date: 2024-06-05, Last modification date: 2024-06-26)

Primary citation

Grba, D.N.,Wright, J.J.,Yin, Z.,Fisher, W.,Hirst, J.
Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I.
Science, 384:1247-1253, 2024

PubMed Abstract: 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.

PubMed: 38870289
DOI: 10.1126/science.ado2075

Experimental method

ELECTRON MICROSCOPY (2.6 Å)