Survey of amino-terminal proteolytic cleavage sites in mitochondrial precursor proteins: leader peptides cleaved by two matrix proteases share a three-amino acid motif.
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.
Hendrick
J P
JP
Yale University School of Medicine, Department of Human Genetics, New Haven, CT 06510.
Hodges
P E
PE
Rosenberg
L E
LE
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*
D004792:Enzyme Precursors; D021382:Protein Sorting Signals; D010447:Peptide Hydrolases