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The Molecular Mechanism of Transport by the Mitochondrial ADP/ATP Carrier

Ruprecht, Jonathan J., King, Martin S., Zögg, Thomas, Aleksandrova, Antoniya A., Pardon, Els, Crichton, Paul G., Steyaert, Jan, Kunji, Edmund R.S.
Cell 2019 v.176 no.3 pp. 435-447.e15
adenosine diphosphate, adenosine triphosphate, amino acids, hydrophobicity, mitochondria
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 a structure 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 conserved hydrophobic residues, and a salt bridge network, braced by tyrosines. 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. Because these features are highly conserved, this mechanism is likely to apply to the whole mitochondrial carrier family.[Display omitted]