INFLUENCE OF THE MATURE PORTION OF A PRECURSOR PROTEIN ON THE MITOCHONDRIAL SIGNAL SEQUENCE

Most mitochondrial proteins are synthesized with an N-terminal signal sequence that targets these proteins to various compartments within th e mitochondria. Signal sequences have been shown to be functional by f using them to a nonmitochondrial passenger protein and observing impor t. In many cases, a signal sequence has been fused to passenger protei ns, such as dihydrofolate reductase, and import occurred. There are, t hough, several unexplained instances in which a signal sequence was at tached to a passenger protein and import was not observed. In this stu dy, the N-terminal 23 residues of the matrix enzyme rhodanese could im port several passenger proteins but were unable to import the mature f orm of mitochondrial aldehyde dehydrogenase (mALDH). However; if these same 23 residues were fused to the middle portion of mALDH, import wa s recovered, suggesting that the rhodanese signal sequence and N termi nus of mALDH were incompatible for import. Circular dichroism data ind icated that a peptide corresponding to the region of fusion between rh odanese and mALDH had less structure than corresponding peptides hom i mported fusion proteins, suggesting that mALDH may alter the helix in the rhodanese signal sequence, thus preventing import.