Structures of mitochondrial transport proteins

We have solved the atomic structures of the mitochondrial ADP/ATP carrier locked in the cytoplasmic state by carboxyatractyloside and in the matrix state by bongkrekic acid. Comparison of the two states explains the function of highly conserved sequence features and reveals that the transport mechanism is unique, involving the coordinated movement of six dynamic elements around a central translocation pathway.

Figure Structural models of the mitochondrial ADP/ATP carrier in the cytoplasmic state (left) and the matrix state (right).

The structures provided important information in support of an alternating-access mechanism [1][2]. The carrier has a single substrate binding site (green hexagon), which has three contact points (black spheres with Roman numerals) and is accessible from the cytoplasm and mitochondrial matrix, respectively. Conformational changes between the cytoplasmic and matrix state, induced by substrate-binding, involve outward rotations of the core elements of each domain (shown in primary colours), opening the matrix side, and inward rotation of the gate elements (shown in grey), closing the cytoplasmic side. The transition from the matrix to the cytoplasmic state involves the same elements operating in reverse.

We are interested in using x-ray crystallography to solve the atomic structures of mitochondrial transport proteins in different states.


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