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Mol Cell. 2019 Aug 16. pii: S1097-2765(19)30552-0. doi: 10.1016/j.molcel.2019.07.022. [Epub ahead of print]

Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.

Author information

1
Institute of Science and Technology Austria, Klosterneuberg 3400, Austria; Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
2
Institute of Science and Technology Austria, Klosterneuberg 3400, Austria; Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, NY 10065, USA.
3
MRC Laboratory of Molecular Biology, Cambridge CB2 OQH, UK.
4
Institute of Science and Technology Austria, Klosterneuberg 3400, Austria. Electronic address: sazanov@ist.ac.at.

Abstract

The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.

KEYWORDS:

bioenergetics; complex i; cryoEM; cytochrome bc1 complex; mitochondria; oxidative phosphorylation; oxidoreductas; protein structure; respiration; supercomplex

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