Kampjut 2020 Science

Kampjut D, Sazanov LA (2020) The coupling mechanism of mammalian respiratory complex I. Science 370:eabc4209. https://doi.org/10.1126/science.abc4209

» PMID: 32972993

Kampjut D, Sazanov Leonid A (2020) Science

Abstract: Mitochondrial complex I couples NADH:ubiquinone oxidoreduction to proton pumping by an unknown mechanism. Here, we present cryo-electron microscopy structures of ovine complex I in five different conditions, including turnover, at resolutions up to 2.3 to 2.5 angstroms. Resolved water molecules allowed us to experimentally define the proton translocation pathways. Quinone binds at three positions along the quinone cavity, as does the inhibitor rotenone that also binds within subunit ND4. Dramatic conformational changes around the quinone cavity couple the redox reaction to proton translocation during open-to-closed state transitions of the enzyme. In the induced deactive state, the open conformation is arrested by the ND6 subunit. We propose a detailed molecular coupling mechanism of complex I, which is an unexpected combination of conformational changes and electrostatic interactions.

• Bioblast editor: Gnaiger E

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Enzyme: Complex I  Regulation: Coupling efficiency;uncoupling