Role of α-subunit of mitochondrial processing peptidase in substrate recognition

Kunitoshi Shimokata, Sakae Kitada, Tadashi Ogishima, Akio Ito

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Mitochondrial processing peptidase is a heterodimer consisting of α- mitochondrial processing peptidase (αMPP) and β-MPP. We investigated the role of α-MPP in substrate recognition using a recombinant yeast MPP. Disruption of amino acid residues between 10 and 129 of the α-MPP did not essentially impair binding activity with β-MPP and processing activity, whereas truncation of the C-terminal 41 amino acids led to a significant loss of binding and processing activity. Several acidic amino acids in the region conserved among the enzymes from various species were mutated to asparagine or glutamine, and effects on processing of the precursors were analyzed. Glu353 is required for processing of malate dehydrogenase, aspartate aminotransferase, and adrenodoxin precursors. Glu377 and Asp378 are needed only for the processing of aspartate aminotransferase and adrenodoxin precursors, both of which have a longer extension peptide than the others studied. However, processing of the yeast α-MPP precursor, which has a short extension peptide of nine amino acids, was not affected by these mutations. Thus, effects of substitution of acidic amino acids on the processing differed with the precursor protein and depended on length of the extension peptides. α-MPP may function as a substrate-recognizing subunit by interacting mainly with basic amino acids at a region distal to the cleavage site in precursors with a longer extension peptide.

Original languageEnglish
Pages (from-to)25158-25163
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number39
DOIs
Publication statusPublished - Sep 25 1998

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Substrates
Processing
Adrenodoxin
Acidic Amino Acids
Peptides
Aspartate Aminotransferases
Amino Acids
Yeast
Yeasts
mitochondrial processing peptidase
Basic Amino Acids
Malate Dehydrogenase
Protein Precursors
Asparagine
Glutamine
Substitution reactions
Mutation
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Role of α-subunit of mitochondrial processing peptidase in substrate recognition. / Shimokata, Kunitoshi; Kitada, Sakae; Ogishima, Tadashi; Ito, Akio.

In: Journal of Biological Chemistry, Vol. 273, No. 39, 25.09.1998, p. 25158-25163.

Research output: Contribution to journalArticle

Shimokata, Kunitoshi ; Kitada, Sakae ; Ogishima, Tadashi ; Ito, Akio. / Role of α-subunit of mitochondrial processing peptidase in substrate recognition. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 39. pp. 25158-25163.
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