Mitochondrial-processing peptidase subunit beta is an enzyme that in humans is encoded by the PMPCBgene.[5][6] This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex.[6]
Structure
The Mitochondrial-processing peptidase subunit beta precursor protein is 54.4 KDa in size and composed of 489 amino acids. The precursor protein contains a 45 amino acid N-terminal fragment as mitochondrion targeting sequence. After cleavage, the matured PMPCB protein is 49.5 KDa in size and has a theoretical pI of 5.76.
Function
Mitochondrial-processing peptidase (MPP) is a metalloendopeptidase, containing two structurally related subunits, mitochondrial-processing peptidase subunit alpha and subunit beta, working in conjunction for its catalytic function.[7] Containing the catalytic site, the beta subunit PMPCB protein cleaves presequences (transit peptides) from mitochondrial protein precursors and releases of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.
The majority of mitochondrial proteins is nuclear-coded, which necessitates proper translocations of mitochondrial targeting proteins. Many mitochondrial proteins are synthesized in a precursor form that contains mitochondria targeting sequence. These precursors are usually cleaved by peptidases and proteases before they arrive their sub-organellar locations. It is likely that altered activity of the mitochondrial processing peptidases is essential to ensure the correct maturation of mitochondrial proteins and that altered activity of these proteases will have dramatic effects in the activity, stability and assembly of mitochondrial proteins. Evidences showed that MPP was involved in the proteolytic maturation of Frataxin, a protein responsible for iron homeostasis.[9] Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder[10][11]
^Teixeira PF, Glaser E (Feb 2013). "Processing peptidases in mitochondria and chloroplasts". Biochimica et Biophysica Acta. 1833 (2): 360–70. doi:10.1016/j.bbamcr.2012.03.012. PMID22495024.
^Koutnikova H, Campuzano V, Koenig M (Sep 1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Human Molecular Genetics. 7 (9): 1485–9. doi:10.1093/hmg/7.9.1485. PMID9700204.
^Branda SS, Yang ZY, Chew A, Isaya G (Jun 1999). "Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae". Human Molecular Genetics. 8 (6): 1099–110. doi:10.1093/hmg/8.6.1099. PMID10332043.
^Cavadini P, Adamec J, Taroni F, Gakh O, Isaya G (Dec 2000). "Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates". The Journal of Biological Chemistry. 275 (52): 41469–75. doi:10.1074/jbc.M006539200. PMID11020385.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Patel PI, Isaya G (Jul 2001). "Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency". American Journal of Human Genetics. 69 (1): 15–24. doi:10.1086/321283. PMID11391483.
Further reading
Koutnikova H, Campuzano V, Koenig M (Sep 1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Human Molecular Genetics. 7 (9): 1485–9. doi:10.1093/hmg/7.9.1485. PMID9700204.
Gordon DM, Shi Q, Dancis A, Pain D (Nov 1999). "Maturation of frataxin within mammalian and yeast mitochondria: one-step processing by matrix processing peptidase". Human Molecular Genetics. 8 (12): 2255–62. doi:10.1093/hmg/8.12.2255. PMID10545606.
Nagao Y, Kitada S, Kojima K, Toh H, Kuhara S, Ogishima T, Ito A (Nov 2000). "Glycine-rich region of mitochondrial processing peptidase alpha-subunit is essential for binding and cleavage of the precursor proteins". The Journal of Biological Chemistry. 275 (44): 34552–6. doi:10.1074/jbc.M003110200. PMID10942759.{{cite journal}}: CS1 maint: unflagged free DOI (link)
