Recognition of mitochondrial protein precursor lacking arginine at position -2 by Mitochondrial Processing Peptidase: Processing of bovine cytochrome p450(SCC) precursor

K. Kojima, E. Yamasaki, S. Kitada, T. Ogishima, A. Ito

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5 Citations (Scopus)

Abstract

Mitochondrial processing peptidase (MPP) specifically cleaves off the N-terminal presequence of the mitochondrial protein precursor. Previous studies demonstrated that Arg at position -2 from the cleavage site, which is found among many precursors, plays a critical role in recognition by MPP. We analyzed the structural elements of bovine cytochrome P450 side-chain cleavage enzyme precursor [pre-P450(SCC)], which has Ala at position -2, for recognition by MPP. Replacement of Ala position -2 of pre-P450(SCC) with Arg resulted in an increase in the cleavage rate. Replacement with Gly caused a reduction in the cleavage rate and the appearance of an additional cleavage site down-stream of the authentic site. A pre-P450(SCC) mutant with Met at position -2 retained cleavage efficiency equal to that of the wild type. These results indicate that -2 Ala of pre-P450(SCC) is recognized by MPP as a determinant for precise cleavage, and that the amino acid at -2 is required to have a straight methylene chain for interaction with the S2 site. The preference for distal basic residues, a hydrophobic residue at +1, and hydroxyl residues at +2 and +3, was almost the same as those of the precursors with Arg at -2, indicating that the recognition mechanism of pre-P450(SCC) by MPP is essentially the same as that of the precursors with Arg at position -2.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalJournal of biochemistry
Volume130
Issue number4
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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