Publication

Article Metrics

Citations


Online attention

Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation

DOI: 10.1038/s41594-020-0473-x DOI Help

Authors: Daniel Grba (The Medical Research Council Mitochondrial Biology Unit) , Judy Hirst (The Medical Research Council Mitochondrial Biology Unit)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 82

State: Published (Approved)
Published: August 2020
Diamond Proposal Number(s): 17057

Abstract: Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. Recent cryo-EM analyses of mammalian and yeast complex I have revolutionized structural and mechanistic knowledge and defined structures in different functional states. Here, we describe a 2.7-Å-resolution structure of the 42-subunit complex I from the yeast Yarrowia lipolytica containing 275 structured water molecules. We identify a proton-relay pathway for ubiquinone reduction and water molecules that connect mechanistically crucial elements and constitute proton-translocation pathways through the membrane. By comparison with known structures, we deconvolute structural changes governing the mammalian ‘deactive transition’ (relevant to ischemia–reperfusion injury) and their effects on the ubiquinone-binding site and a connected cavity in ND1. Our structure thus provides important insights into catalysis by this enigmatic respiratory machine.

Journal Keywords: Biochemistry; Electron microscopy; Enzyme mechanisms; Structural biology

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios IV-Titan Krios IV at Diamond

Added On: 19/08/2020 14:24

Discipline Tags:

Biochemistry Catalysis Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)