Title | Mitochondrial carriers in the cytoplasmic state have a common substrate binding site. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Robinson, AJ, Kunji, ERS |
Journal | Proc Natl Acad Sci U S A |
Volume | 103 |
Issue | 8 |
Pagination | 2617-22 |
Date Published | 2006 Feb 21 |
ISSN | 0027-8424 |
Keywords | Amino 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 |
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. |
DOI | 10.1073/pnas.0509994103 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
Citation Key | 10.1073/pnas.0509994103 |
PubMed ID | 16469842 |
PubMed Central ID | PMC1413793 |
Grant List | MC_U105663139 / / Medical Research Council / United Kingdom MC_U105674181 / / Medical Research Council / United Kingdom |