title: Divergent Hsc70 binding properties of mitochondrial and cytosolic aspartate aminotransferase. Implications for their segregation to different cellular compartments.
abstract: Cytosolic Hsc70 discriminates between the homologous mitochondrial and cytosolic isozymes of aspartate aminotransferase, binding exclusively the mitochondrial form. By screening a library of synthetic peptides spanning the sequence of the mitochondrial enzyme, we have identified binding sites in this polypeptide that interact with Hsc70. These potential binding sites are scattered over the entire sequence and map to secondary structure elements, particularly the alpha-helix, that are partly exposed on the surface of the native protein. Several peptides corresponding to analogous positions in the cytosolic enzyme sequence do not bind to Hsc70. Phylogenetic analyses suggest that Hsc70 binding sequences have diverged as a consequence of biochemical specialization ensuring differential interaction of each isozyme with the cellular machinery in charge of protein folding and translocation.
authors.affiliation: Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110, USA.
authors.forename: A
authors.initials: A
authors.lastname: Artigues
authors.forename: D L
authors.initials: DL
authors.lastname: Crawford
authors.forename: A
authors.initials: A
authors.lastname: Iriarte
authors.forename: M
authors.initials: M
authors.lastname: Martinez-Carrion
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002451:Cell Compartmentation; D003600:Cytosol / Q000201:enzymology*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D001219:Aspartate Aminotransferases