The molecular mechanism of transport by the mitochondrial ADP/ATP carrier

Ruprecht, Jonathan J., King, Martin S., Zögg, Thomas, Aleksandrova, Antoniya A., Pardon, Els, Crichton, Paul G. ORCID:, 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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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
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Depositing User: LivePure Connector
Date Deposited: 08 Jan 2019 09:30
Last Modified: 19 Oct 2023 02:20
DOI: 10.1016/j.cell.2018.11.025

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