Daniel N Grba / John J Wright / Zhan Yin / William Fisher / Judy Hirst /
PubMed 要旨
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 ...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.
EMDB-18054: Inward-facing, slack proteoliposome complex I at 3.1 A. Initially purified in DDM. PDB-8q0j: Inward-facing, slack proteoliposome complex I at 3.8 A. Initially purified in DDM. 手法: EM (単粒子) / 解像度: 3.8 Å
EMDB-18059: Outward-facing, slack proteoliposome complex I at 3.1 A. Initially purified in DDM. PDB-8q0q: Outward-facing, slack proteoliposome complex I at 3.6 A. Initially purified in DDM 手法: EM (単粒子) / 解像度: 3.6 Å
EMDB-18066, PDB-8q1p: Inward-facing, open2 proteoliposome complex I at 2.9 A, after deactivation treatment. Initially purified in LMNG. 手法: EM (単粒子) / 解像度: 2.9 Å
EMDB-18067, PDB-8q1u: Inward-facing, open1 proteoliposome complex I at 3.3 A, after deactivation treatment. Initially purified in LMNG. 手法: EM (単粒子) / 解像度: 3.3 Å
EMDB-18068, PDB-8q1y: Outward-facing, open2 proteoliposome complex I at 2.6 A, after deactivation treatment. Initially purified in LMNG. 手法: EM (単粒子) / 解像度: 2.6 Å
EMDB-18069, PDB-8q25: Outward-facing, open1 proteoliposome complex I at 2.8 A, after deactivation treatment. Initially purified in LMNG. 手法: EM (単粒子) / 解像度: 2.8 Å