Divergent Hsc70 binding properties of mitochondrial and cytosolic aspartate aminotransferase - Implications for their segregation to different cellular compartments

Cytosolic Hsc70 discriminates between the homologous mitochondrial and cyto solic isozymes of aspartate aminotransferase, binding exclusively the mitoc hondrial form. By screening a library of synthetic peptides spanning the se quence of the mitochondrial enzyme, we have identified binding sites in thi s polypeptide that interact with Hsc70. These potential binding sites are s cattered 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 t he cytosolic enzyme sequence do not bind to Hsc70. Phylogenetic analyses su ggest that Hsc70 binding sequences have diverged as a consequence of bioche mical specialization ensuring differential interaction of each isozyme with the cellular machinery in charge of protein folding and translocation.