The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier.
King, Martin S
Crichton, Paul G
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Ruprecht, J., King, M. S., Zögg, T., Aleksandrova, A. A., Pardon, E., Crichton, P. G., Steyaert, J., & et al. (2019). The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier.. Cell, 176 (3), 435-447.e15. https://doi.org/10.1016/j.cell.2018.11.025
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 one 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 a salt bridge network, braced by tyrosines, and conserved hydrophobic residues. ￼￼1 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. Since these features are highly conserved, this mechanism is likely to apply to the whole mitochondrial carrier family.
Cytoplasm, Mitochondria, Saccharomyces cerevisiae, Bongkrekic Acid, Mitochondrial ADP, ATP Translocases, Saccharomyces cerevisiae Proteins, Mitochondrial Membrane Transport Proteins, Adenosine Diphosphate, Adenosine Triphosphate, Binding Sites, Amino Acid Sequence, Protein Conformation, Protein Structure, Secondary, Biological Transport, Models, Molecular
External DOI: https://doi.org/10.1016/j.cell.2018.11.025
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287654