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., 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:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	08 Jan 2019 09:30
Last Modified:	06 Feb 2025 08:11
URI:	https://ueaeprints.uea.ac.uk/id/eprint/69463
DOI:	10.1016/j.cell.2018.11.025

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