Mammalian mitochondrial intermediate peptidase: Structure/function analysis of a new homologue from Schizophyllum commune and relationship to thimet oligopeptidases

Journal Article · Thu Aug 10 04:00:00 EDT 1995 · Genomics

DOI:https://doi.org/10.1006/geno.1995.1174· OSTI ID:390667

Isaya, G; Sakati, W R; Rollins, R A ^[1]

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1. Yale Univ. School of Medicine, New Haven, CT (United States); and others

Mitochondrial intermediate peptidase (MIP) is a component of the mitochondrial protein import machinery required for maturation of nuclear-encoded precursor proteins targeted to the mitochondrial matrix or inner membrane. We previously characterized this enzyme in rat (RMIP) and Saccharomyces cerevisiae (YMIP) and showed that MIP activity is essential for mitochondrial function in yeast. We have now defined the structure of a new MIP homologue (SMIP) from the basidiomycete fungus Schizophyllum commune. SMIP includes 4 exons of 523, 486, 660, and 629 bp separated by 3 short introns. The predicted SMIP, YMIP, and RMIP sequences share 31-37% identity and 54-57% similarity over 700 amino acids. When SMIP and RMIP were expressed in a yeast mip1{Delta} mutant, they were both able to rescue the respiratory-deficient phenotype caused by genetic inactivation of YMIP, indicating that the function of this enzyme is conserved in eukaryotes. Moreover, the MIP sequences show 20-24% identity and 40-47% similarity to a family of oligopeptidases from bacteria, yeast, and mammals. MIP and these proteins are characterized by a highly conserved motif, F-H-E-X-G-H-(X){sub 12}-G-(X){sub 5}-D-(X){sub 2}-E-X-P-S-(X){sub 3}-E-X, centered around a zinc-binding site and appear to represent a new family of genes associated with proteolytic processing in the mitochondrial and cytosolic compartments. 48 refs., 8 figs.

• OSTI ID: 390667
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 28; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
DNA SEQUENCING
ENZYME ACTIVITY
FUNGI
MAMMALS
MITOCHONDRIA
MUTANTS
NONSPECIFIC PEPTIDASES
PHENOTYPE
STRUCTURE-ACTIVITY RELATIONSHIPS