Substrate recognition by mitochondrial processing peptidase toward the malate dehydrogenase precursor

Kunitoshi Shimokata, Takenori Nishio, Myeong Cheol Song, Sakae Kitada, Tadashi Ogishima, Akio Ito

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23 Citations (Scopus)


Mitochondrial processing peptidase (MPP) cleaves the extension peptides of precursor proteins newly imported into the mitochondria. Using synthetic oligopeptides modeled on the extension peptide of malate dehydrogenase, the critical elements of the substrate for the processing of MPP were determined. In the present study, we constructed mutant precursors and compared the processing reaction with that of the peptide substrates to confirm the validity of use of peptide substrates. In both cases, the arginine residue presents at a proximal (-2) position relative to the processing site proved to be important for the processing. The distal arginine residue at position 7 was replaceable with alanine with no significant loss in cleavage efficiency if the precursor protein contained two consecutive arginine residues at a proximal position, although the arginine residue at a position 7 was indispensable in the model peptide. The proline residue, lying between the distal and proximal arginine residues, which is assumed to break a continuous α-helix region in the extension peptide, was needed for the processing. This peptidase has a preference for aromatic amino acids at the P1' site. These results were essentially the same as those obtained with model peptides except for the role of the distal arginine. We also found that amino acids at P2' and P3' sites had some effects on the processing. Thus we concluded that an effective combination of model peptides with precursor proteins is needed for the studies on MPP responsible substrate-recognition mechanisms.

Original languageEnglish
Pages (from-to)1019-1023
Number of pages5
JournalJournal of biochemistry
Issue number5
Publication statusPublished - Nov 1997

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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