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Mitochondrial carriers in the cytoplasmic state have a common substrate binding site.

ABSTRACT: Mitochondrial carriers link biochemical pathways in the cytosol and mitochondrial matrix by transporting substrates across the inner mitochondrial membrane. Substrate recognition is specific for each carrier, but sequence similarities suggest the carriers have similar structures and mechanisms of substrate translocation. By considering conservation of amino acids, distance and chemical constraints, and by modeling family members on the known structure of the ADP/ATP translocase, we have identified a common substrate binding site. It explains substrate selectivity and proton coupling and provides a mechanistic link to carrier opening by substrate-induced perturbation of the salt bridges that seal the pathway to and from the mitochondrial matrix. It enables the substrate specificity of uncharacterized mitochondrial carriers to be predicted.

SUBMITTER: Robinson AJ

PROVIDER: S-EPMC1413793 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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Mitochondrial carriers in the cytoplasmic state have a common substrate binding site.

Robinson Alan J AJ Kunji Edmund R S ER

Proceedings of the National Academy of Sciences of the United States of America 20060209 8

Mitochondrial carriers link biochemical pathways in the cytosol and mitochondrial matrix by transporting substrates across the inner mitochondrial membrane. Substrate recognition is specific for each carrier, but sequence similarities suggest the carriers have similar structures and mechanisms of substrate translocation. By considering conservation of amino acids, distance and chemical constraints, and by modeling family members on the known structure of the ADP/ATP translocase, we have identifi ...[more]

PMID: 16469842

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