A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum.
BACKGROUND
The malarial parasite, Plasmodium falciparum (Pf), is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined.


RESULTS
We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs), compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90). PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid.


CONCLUSIONS
This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.
Dobson
S
S
Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, 307 University Blvd, Mobile, Alabama 36688-0002, USA. sdobson@wfubmc.edu
Kar
B
B
Kumar
R
R
Adams
B
B
Barik
S
S
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010455:Peptides; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D018841:HSP90 Heat-Shock Proteins; D009687:Nuclear Proteins; D010455:Peptides; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5