The carboxyl-terminal third of the dicarboxylate carrier is crucial for productive association with the inner membrane twin-pore translocase.
The carrier proteins of the mitochondrial inner membrane consist of three structurally related tandem repeats (modules). Several different, and in some cases contradictory, views exist on the role individual modules play in carrier transport across the mitochondrial membranes and how they promote protein insertion into the inner membrane. Thus, by use of specific translocation intermediates, we performed a detailed analysis of carrier biogenesis and assessed the physical association of carrier modules with the inner membrane translocation machinery. Here we have reported that each module of the dicarboxylate carrier contains sufficient targeting information for its transport across the outer mitochondrial membrane. The carboxyl-terminal module possesses major targeting information to facilitate the direct binding of the carrier protein to the inner membrane twin-pore translocase and subsequent insertion into the inner membrane in a membrane potential-dependent manner. We concluded that, in this case, a single structural repeat can drive inner membrane insertion, whereas all three related units contribute targeting information for outer membrane translocation.
Brandner
Katrin
K
Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany.
Rehling
Peter
P
Truscott
Kaye N
KN
D029382:Dicarboxylic Acid Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism; D008564:Membrane Potentials; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D029382:Dicarboxylic Acid Transporters; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C102549:TIM22 protein, S cerevisiae