title: Survey of amino-terminal proteolytic cleavage sites in mitochondrial precursor proteins: leader peptides cleaved by two matrix proteases share a three-amino acid motif.
abstract: We have compiled sequences of precursor proteins for 50 mitochondrial proteins for which the mature amino terminus has been determined by amino acid sequence analysis. Included in this set are 8 precursors that have leader peptides that are cleaved in two places by mitochondrial matrix proteases. When these eight leader peptides are aligned and compared, a highly conserved three-amino acid motif is identified as being common to this class of leader peptides. This motif includes an arginine at position -10, a hydrophobic residue at position -8, and serine, threonine, or glycine at position -5 relative to the mature amino terminus. The initial cleavage of these peptides by matrix processing protease occurs within the motif, between residues at -9 and -8, such that arginine at position -10 is at position -2 relative to the cleaved bond. The rest of the motif is within the octapeptide removed by subsequent cleavage catalyzed by intermediate-specific protease. An additional 14 leader peptides in this collection (all of those that contain an arginine at -10) conform to this motif. Assuming that these 14 precursors are matured in two steps, we compared the internal cleavage sites at position -8 with the ends of the other 30 leader peptides in the collection. We find that 74% of matrix processing protease cleavage sites follow an arginine at position -2 relative to cleavage.
authors.affiliation: Yale University School of Medicine, Department of Human Genetics, New Haven, CT 06510.
authors.forename: J P
authors.initials: JP
authors.lastname: Hendrick
authors.forename: P E
authors.initials: PE
authors.lastname: Hodges
authors.forename: L E
authors.initials: LE
authors.lastname: Rosenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004792:Enzyme Precursors / Q000235:genetics*; D006801:Humans; D007256:Information Systems; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics*
chemical_list: D004792:Enzyme Precursors; D021382:Protein Sorting Signals; D010447:Peptide Hydrolases