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

TitleMitochondrial carriers in the cytoplasmic state have a common substrate binding site.
Publication TypeJournal Article
Year of Publication2006
AuthorsRobinson, AJ, Kunji, ERS
JournalProc Natl Acad Sci U S A
Date Published2006 Feb 21
KeywordsAmino Acid Sequence, Binding Sites, Carrier Proteins, Cytoplasm, Guanosine Diphosphate, Guanosine Triphosphate, Humans, Ion Channels, Membrane Proteins, Mitochondrial ADP, ATP Translocases, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Models, Molecular, Molecular Sequence Data, Phosphate Transport Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Uncoupling Protein 1

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.0509994103
PubMed ID16469842
PubMed Central IDPMC1413793
Grant ListMC_U105663139 / / Medical Research Council / United Kingdom
MC_U105674181 / / Medical Research Council / United Kingdom