Biology:PMPCA

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Mitochondrial-processing peptidase subunit alpha is an enzyme that in humans is encoded by the PMPCA gene.[1][2][3] This gene PMPCA encoded a protein that is a member of the peptidase M16 family. 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.

Structure

The Mitochondrial-processing peptidase subunit alpha precursor protein is 58.2 KDa in size and composed of 525 amino acids. The precursor protein contains a 33 amino acid N-terminal fragment as mitochondrion targeting sequence. After cleavage, the matured PMPCA protein is 54.6 KDa in size and has a theoretical pI of 5.88.

Function

Mitochondrial-processing peptidase (MPP) is a metalloendopeptidase, containing two structurally related subunits, Subunit alpha and mitochondrial-processing peptidase subunit beta, working in conjunction for its catalytic function.[4] 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.

Interactions

As the alpha subunit of Mitochondrial-processing peptidase, PMPCA forms a heterodimer with the subunit PMPCB.

Clinical significance

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.[5] Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder[6][7]

References

  1. "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res 2 (4): 167–74, 199–210. Mar 1996. doi:10.1093/dnares/2.4.167. PMID 8590280. 
  2. "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res 2 (1): 37–43. Jul 1995. doi:10.1093/dnares/2.1.37. PMID 7788527. 
  3. "Entrez Gene: PMPCA peptidase (mitochondrial processing) alpha". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23203. 
  4. "Processing peptidases in mitochondria and chloroplasts". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833 (2): 360–70. Feb 2013. doi:10.1016/j.bbamcr.2012.03.012. PMID 22495024. 
  5. "Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae". Human Molecular Genetics 8 (6): 1099–110. Jun 1999. doi:10.1093/hmg/8.6.1099. PMID 10332043. 
  6. "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. Dec 2000. doi:10.1074/jbc.M006539200. PMID 11020385. 
  7. "Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency". American Journal of Human Genetics 69 (1): 15–24. Jul 2001. doi:10.1086/321283. PMID 11391483. 

Further reading