In 2014, we solved the structures of the yeast mitochondrial ADP/ATP carriers Aac2p and Aac3p, which are transport proteins that are involved in the exchange of ADP and ATP across the mitochondrial inner membrane under aerobic and anaerobic conditions, respectively.
Figure Atomic structures of the yeast ADP/ATP carrier Aac2p (left) and the yeast ADP/ATP carrier Aac3p (right).
The structures provided important information in support of an alternating-access mechanism . All of the residues that form the matrix and cytoplasmic salt bridge network, flanking the central cavity, are now fully resolved. Analyses of the domain structures and properties of the inter-domain interfaces indicate that the interconversions between states involve the movement of the even-numbered α-helices across the surfaces of the odd-numbered α-helices by rotation of the domains. The odd-numbered α-helices have an L-shape, with proline or serine residues at the kinks, which functions as a lever-arm, coupling the substrate-induced disruption of the matrix salt bridge network to the formation of the cytoplasmic salt bridge network. The expression, purification and crystallisation approaches used in this work have opened the way to solve structures of other members of this protein family.
We are interested in using x-ray crystallography to solve the atomic structures of mitochondrial transport proteins in different states.
- (2014) Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism. Proc Natl Acad Sci U S A 111, E426-34