Mitochondrial ADP/ATP carrier: preventing conformational changes by point mutations inactivates nucleotide transport activity.

The mitochondrial ADP/ATP carrier (Ancp) is a paradigm of the mitochondrial carrier family (MCF); its members allow metabolic fluxes between mitochondria and the cytosol. The members of the MCF share numerous structural and functional characteristics. Ancp is very specifically inhibited by two classes of compounds, which stabilize the carrier in two different conformations involved in nucleotide transport.

Unambiguous structure of atractyloside and carboxyatractyloside.

Atractyloside (ATR) was characterized in 1868 and until now structural studies on diterpenic moiety had been done through the characterization of ATR derivatives; while the glycosidic moiety seemed to be a β-D-glucopyranose a recent crystal structure of the mitochondrial ATP/ADP carrier in complex with CATR showed an α-D-glucopyranose. We decided to re-examine the ATR and CATR structures by crystallographic study of ATR.

The transmembrane prolines of the mitochondrial ADP/ATP carrier are involved in nucleotide binding and transport and its biogenesis.

The mitochondrial ADP/ATP carrier (Ancp) is a paradigm of the mitochondrial carrier family, which allows cross-talk between mitochondria, where cell energy is mainly produced, and cytosol, where cell energy is mainly consumed. The members of this family share numerous structural and functional characteristics. Resolution of the atomic structure of the bovine Ancp, in a complex with one of its specific inhibitors, revealed interesting features and suggested the involvement of some particular residues in the movements of the protein to perform translocation of nucleotides from one side of the membrane to the other.

Native membrane proteins vs. yeast recombinant: an example: the mitochondrial ADP/ATP carrier.

The mitochondrial ADP/ATP carrier (Ancp) has long been a paradigm for studies of the mitochondrial carrier family due to, among other properties, its natural abundance and the existence of specific inhibitors, namely, carboxyatractyloside (CATR) and bongkrekic acid (BA), which lock the carrier under distinct and stable conformations. Bovine Anc1p isolated in complex with CATR in the presence of an aminoxyde detergent (LAPAO) was crystallized and its 3D structure determined. It is the first mitochondrial carrier structure resolved at high resolution (2.