Processing peptidase

Its length can vary from 30 to more than 100 residues. It is rich in serine and threonine but deficient in acidic residues. It is not clear whether it has the three-domain structure like the signal peptide (von Heijne et al., 1989). Recently, a chloroplast-processing enzyme was identified as the general stromal processing peptidase (Richter and Lamppa, 1998). 

Luciano, P., and Geli, V. (1996). The mitochondrial processing peptidase function and specificity. Experientia 52, 1077-1082. 

Richter, S., and Lamppa, G. (1998). A chloroplast processing enzyme functions as the general stromal processing peptidase. Proc. Natl. Acad. Sci. U.S.A. 95, 7463-7468. 

Song, M.-C., Shimokata, K, Kitada, S., Ogishima, T., and Ito, A. (1996). Role of basic amino acids in the cleavage of synthetic peptide substrate by mitochondrial processing peptidase./. Biochem.. (Tokyo) 120, 1163-1166. 

This zinc-dependent enzyme [EC 3.4.24.59] of the peptidase M3 family catalyzes the hydrolysis of a peptide bond such that there is a release of an N-terminal octa-peptide at the second stage of processing of some proteins imported into the mitochondrion. The natural substrates are precursor proteins that already have been processed by the mitochondrial processing peptidase. 

This a-helix is amphipathic, containing patches of positively charged and hydrophobic amino acids, respectively, on opposite surfaces of the theoretical cylinder. The presequence is usually processed by the mitochondrial processing peptidase (MPP) and the mature protein is sorted to either the matrix, or to the inner membrane if it bears a hydrophobic stop-transfer sequence. Some mitochondrial proteins, mostly destined to the membranes, do not have cleavable N-terminal presequences but have internal targeting signals that are not well characterized (Pfanner and Geissler 2001). 

Fig-i Mitochondrial protein import machinery as defined in S. cerevisiae. TOM translo-case of the outer mitochondrial membrane SAM sorting and assembly machinery TIM translocase of the inner mitochondrial membrane MIA mitochondrial IMS import and assembly machine PAM presequence translocase associated motor IMP inner membrane protease MPP mitochondrial processing peptidase. The numbers on the individual Tom, Sam, Tim or Pam components represent their approximate molecular masses in kDa. See text for mechanistic details. Adopted from Dolezal et al. 2006... 

Mitochondrial processing peptidase (J-MPP MSIISRY AVPQISKLSNGVRV() Dolezal et al. (2005)... 

The mitochondrial processing peptidase is an essential zinc-dependent met-allopeptidase (Yaffe et al. 1985 Luciano and Geli 1996 Gakh et al. 2002 Nomura et al. 2006). It cleaves the N-terminal presequence from precursors to matrix-targeted proteins, and from precursors destined for the inner mem-... 

Gabriel et al. (2007) Novel mitochondrial intermembrane space proteins as substrates of the MIA import pathway. J Mol Biol 365 612-620 Gakh O, Cavadini P, Isaya G (2002) Mitochondrial processing peptidases. Biochim Biophys Acta 1592 63-77... 

Nomura H, Athauda SB, Wada H, Maruyama Y, Takahashi K, Inoue H (2006) Identification and reverse genetic analysis of mitochondrial processing peptidase and the core protein of the cytochrome bcl complex of Caenorhabditis elegans, a model parasitic nematode. J Biochem (Tokyo) 139 967-979... 

After translocation into the mitosome, the N-terminal presequences of mitosomal proteins are cleaved off, most likely by a peptidase that is homologous to the mitochondrial processing peptidase (MPP). The MPP is a matrix-localized metallopeptidase with a zinc binding motif His-X-X-Glu-His that is conserved in the putative mitosomal processing peptidase reported in G. intestinalis (Dolezal et al. 2005). 

Mitochondria arise by division and growth of preexisting mitochondria. Because they synthesize only a few proteins and RNA molecules, they must import many proteins and other materials from the cytoplasm. A mitochondrion contains at least 100 proteins that are encoded by nuclear genes.50,50a The mechanisms by which proteins are taken up by mitochondria are complex and varied. Many of the newly synthesized proteins carry, at the N terminus, presequences that contain mitochondrial targeting signals51-53 (Chapter 10). These amino acid sequences often lead the protein to associate with receptor proteins on the outer mitochondrial membrane and subsequently to be taken up by the mitochondria. While the targeting sequences are usually at the N terminus of a polypeptide, they are quite often internal. The N-terminal sequences are usually removed by action of the mitochondrial processing peptidase (MPP) in... 

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