6ZTQ

Cryo-EM structure of respiratory complex I from Mus musculus inhibited by piericidin A at 3.0 A

Summary for 6ZTQ

• Entry DOI: 10.2210/pdb6ztq/pdb
• Related: 6ZR2
• EMDB information: 11377 11424 11425
• Descriptor: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 6, NADH-ubiquinone oxidoreductase chain 4L, ... (55 entities in total)
• Functional Keywords: nadh, ubiquinone, complex i, oxidoreductase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 45
• Total formula weight: 1072740.43

Authors

Bridges, H.R.,Blaza, J.N.,Agip, A.N.A.,Hirst, J. (deposition date: 2020-07-20, release date: 2020-10-21, Last modification date: 2025-04-09)

Primary citation

Bridges, H.R.,Fedor, J.G.,Blaza, J.N.,Di Luca, A.,Jussupow, A.,Jarman, O.D.,Wright, J.J.,Agip, A.A.,Gamiz-Hernandez, A.P.,Roessler, M.M.,Kaila, V.R.I.,Hirst, J.
Structure of inhibitor-bound mammalian complex I.
Nat Commun, 11:5261-5261, 2020

PubMed Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I.

PubMed: 33067417
DOI: 10.1038/s41467-020-18950-3

Experimental method

ELECTRON MICROSCOPY (3 Å)