Mitochondrial carriers function as monomers

Kunji, Edmund R. S. and Crichton, Paul G. ORCID: (2010) Mitochondrial carriers function as monomers. Biochimica et Biophysica Acta - Bioenergetics, 1797 (6-7). pp. 817-831. ISSN 0005-2728

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Mitochondrial carriers link biochemical pathways in the mitochondrial matrix and cytosol by transporting metabolites, inorganic ions, nucleotides and cofactors across the mitochondrial inner membrane. Uncoupling proteins that dissipate the proton electrochemical gradient also belong to this protein family. For almost 35. years the general consensus has been that mitochondrial carriers are dimeric in structure and function. This view was based on data from inhibitor binding studies, small-angle neutron scattering, electron microscopy, differential tagging/affinity chromatography, size-exclusion chromatography, analytical ultracentrifugation, native gel electrophoresis, cross-linking experiments, tandem-fusions, negative dominance studies and mutagenesis. However, the structural folds of the ADP/ATP carriers were found to be monomeric, lacking obvious dimerisation interfaces. Subsequently, the yeast ADP/ATP carrier was demonstrated to function as a monomer. Here, we revisit the data that have been published in support of a dimeric state of mitochondrial carriers. Our analysis shows that when critical factors are taken into account, the monomer is the only plausible functional form of mitochondrial carriers. We propose a transport model based on the monomer, in which access to a single substrate binding site is controlled by two flanking salt bridge networks, explaining uniport and strict exchange of substrates.

Item Type: Article
Uncontrolled Keywords: detergent,lipid,membrane protein,oligomeric state,protein-protein interaction,transport mechanism
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: Pure Connector
Date Deposited: 03 Nov 2016 11:00
Last Modified: 19 Oct 2023 01:51
DOI: 10.1016/j.bbabio.2010.03.023

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