Hendrick J P, Hodges P E, Rosenberg L E
Yale University School of Medicine, Department of Human Genetics, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4056-60. doi: 10.1073/pnas.86.11.4056.
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.
我们已经汇编了50种线粒体蛋白前体蛋白的序列，这些蛋白的成熟氨基末端已通过氨基酸序列分析确定。该集合中包括8种前体蛋白，它们具有前导肽，这些前导肽会被线粒体基质蛋白酶在两个位置切割。当将这8种前导肽进行比对和比较时，发现一个高度保守的三氨基酸基序是这类前导肽所共有的。该基序包括相对于成熟氨基末端在-10位的精氨酸、在-8位的疏水残基以及在-5位的丝氨酸、苏氨酸或甘氨酸。这些肽被基质加工蛋白酶的初始切割发生在该基序内，在-9和-8位的残基之间，使得-10位上的精氨酸相对于切割后的键处于-2位。该基序的其余部分位于后续由中间特异性蛋白酶催化切割去除的八肽内。该集合中的另外14种前导肽（所有在-10位含有精氨酸的那些）符合该基序。假设这14种前体蛋白分两步成熟，我们将-8位的内部切割位点与该集合中其他30种前导肽的末端进行了比较。我们发现74%的基质加工蛋白酶切割位点在相对于切割位置的-2位处有一个精氨酸。
