Abstract
SummaryMitochondrial 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.Video
Highlights
Solute transport across the impermeable mitochondrial inner membrane is essential for the function and survival of eukaryotic cells
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
Summary
The structure of the matrix-open state of the mitochondrial ADP/ATP carrier reveals its transport mechanism, which involves rotation of six structural elements around a central substratebinding site. Highlights d Structure of the matrix-open state of the mitochondrial ADP/ ATP carrier solved d The inhibitor bongkrekic acid locks the state by occupying the substrate-binding site d Conformational changes during transport are highly dynamic, using six mobile elements d Roles of all conserved sequence features in mitochondrial carriers are explained. 2019, Cell 176, 435–447 January 24, 2019 a 2018 The Author(s).
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