STRUCTURE OF THE SIGNAL SEQUENCES FOR 2 MITOCHONDRIAL MATRIX PROTEINSTHAT ARE NOT PROTEOLYTICALLY PROCESSED UPON IMPORT

The N-terminal sequences of rhodanese and 3-oxoacyl-CoA thiolase, two mitochondrial matrix proteins that are not proteolytically processed u pon import, have been studied by NMR and CD spectroscopy. In aqueous t rifluoroethanol, in the presence of micelles, and in the presence of s mall unilamellar vesicles (SUVs), these peptides form alpha-helical st ructures beginning near the N-terminus and extending, continuously, fo r at least three helical turns. This result is consistent with a previ ous finding that a mutant rat liver mitochondrial aldehyde dehydrogena se signal sequence we designed, which formed a continuous alpha-helix, could successfully direct protein import but was not proteolytically processed (Thornton, K., Wang, Y., Weiner, H., & Gorenstein, D. G. (19 93) J. Biol. Chem. 268, 19906-19914). From these three examples, a mod el is developed which suggests that a mitochondrial signal sequence th at has an N-terminal alpha-helix longer than 11 residues can take on t he necessary conformation to be imported but cannot adopt the necessar y conformation to be processed.