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

Preview

PDF (Published Version) - Published Version Available under License Creative Commons Attribution. Download (13MB) | Preview

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
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	08 Jan 2019 09:30
Last Modified:	12 Jun 2021 10:08
URI:	https://ueaeprints.uea.ac.uk/id/eprint/69463
DOI:	10.1016/j.cell.2018.11.025

Actions (login required)

View Item