Structural approaches of the mitochondrial carrier family.
The transport of solutes across the inner mitochondrial membrane is highly selective and necessitates membrane proteins mainly from the mitochondrial carrier family (MCF). These carriers are required for the transport of a variety of metabolites implicated in all the important processes occurring within the mitochondrial matrix. Due to its high abundance, the ADP/ATP carrier (AAC) is the member of the family that was studied most. It is the first mitochondrial carrier for which a high-resolution X-ray structure is known. The carrier was crystallized in the presence of a strong inhibitor, the carboxyatractyloside (CATR). The structure gives an insight not only into the overall fold of mitochondrial carriers in general but also into atomic details of the AAC in a conformation that is open toward the intermembrane space (IMS). Molecular dynamics simulations indicate the first events occurring to the carrier after the binding of ADP. A careful analysis of the primary sequences of all the carriers in light with the structure highlights properties of the protein that are related to the substrate.
Nury
Hugues
H
Institut Pasteur, Unit if Structural Dynamics of Macromolecules, CNRS, URA 2185, Paris, France.
Blesneac
Iulia
I
Ravaud
Stephanie
S
Pebay-Peyroula
Eva
E
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D001278:Atractyloside / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D001278:Atractyloside; D000244:Adenosine Diphosphate; D000226:Mitochondrial ADP, ATP Translocases; C003853:carboxyatractyloside