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Ruprecht, Jonathan J., King, Martin S., Zögg, Thomas, Aleksandrova, Antoniya A., Pardon, Els, Crichton, Paul G. 
ORCID: https://orcid.org/0000-0003-3786-8359, Steyaert, Jan and Kunji, Edmund R. S.
(2019)
The molecular mechanism of transport by the mitochondrial ADP/ATP carrier.
Cell, 176 (3).
435-447.e15.
ISSN 0092-8674
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Abstract
Mitochondrial ADP/ATP carriers transport ADP into the mitochondrial matrix for ATP synthesis, and ATP out to fuel the cell, by cycling between cytoplasmic-open and matrix-open states. The structure of the cytoplasmic-open state is known, but it has proved difficult to understand the transport mechanism in the absence of a structure in the matrix-open state. Here, we describe the structure of the matrix-open state locked by bongkrekic acid bound in the ADP/ATP-binding site at the bottom of the central cavity. The cytoplasmic side of the carrier is closed by conserved hydrophobic residues, and a salt bridge network, braced by tyrosines. Glycine and small amino acid residues allow close-packing of helices on the matrix side. Uniquely, the carrier switches between states by rotation of its three domains about a fulcrum provided by the substrate-binding site. Because these features are highly conserved, this mechanism is likely to apply to the whole mitochondrial carrier family.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved. |
| Uncontrolled Keywords: | adenine nucleotide translocator,adenine nucleotide translocase,bongkrekate,cardiolipin,induced fit,transport mechanism,bioenergetics |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 08 Jan 2019 09:30 |
| Last Modified: | 19 Oct 2023 02:20 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/69463 |
| DOI: | 10.1016/j.cell.2018.11.025 |
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