title: Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics.
abstract: BACKGROUND
  Although the complete genome sequences of a large number of organisms have been determined, the exact proteomes need to be characterized. More specifically, the extent to which post-translational processes such as proteolysis affect the synthesized proteins has remained unappreciated. We examined this issue in selected protein phosphatases of the protease-rich malaria parasite, Plasmodium falciparum.
  
  
  RESULTS
  P. falciparum encodes a number of Ser/Thr protein phosphatases (PP) whose catalytic subunits are composed of a catalytic core and accessory domains essential for regulation of the catalytic activity. Two examples of such regulatory domains are found in the Ca+2-regulated phosphatases, PP7 and PP2B (calcineurin). The EF-hand domains of PP7 and the calmodulin-binding domain of PP2B are essential for stimulation of the phosphatase activity by Ca+2. We present biochemical evidence that P. falciparum generates these full-length phosphatases as well as their catalytic cores, most likely as intermediates of a proteolytic degradation pathway. While the full-length phosphatases are activated by Ca+2, the processed cores are constitutively active and either less responsive or unresponsive to Ca+2. The processing is extremely rapid, specific, and occurs in vivo.
  
  
  CONCLUSIONS
  Post-translational cleavage efficiently degrades complex full-length phosphatases in P. falciparum. In the course of such degradation, enzymatically active catalytic cores are produced as relatively stable intermediates. The universality of such proteolysis in other phosphatases or other multi-domain proteins and its potential impact on the overall proteome of a cell merits further investigation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, Mobile, USA 36688-0002. rkumar@usamail.usouthal.edu
authors.forename: Rajinder
authors.initials: R
authors.lastname: Kumar
authors.forename: Alla
authors.initials: A
authors.lastname: Musiyenko
authors.forename: Anja
authors.initials: A
authors.lastname: Oldenburg
authors.forename: Brian
authors.initials: B
authors.lastname: Adams
authors.forename: Sailen
authors.initials: S
authors.lastname: Barik
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D008288:Malaria; D016778:Malaria, Falciparum / Q000201:enzymology*; D008969:Molecular Sequence Data; D010271:Parasites / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis* / Q000737:chemistry; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000737:chemistry; D040901:Proteomics; D015800:Protozoan Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment / Q000379:methods
chemical_list: D015800:Protozoan Proteins; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C494121:Rdg7 protein, Plasmodium falciparum; D010447:Peptide Hydrolases