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Plasmodium protein phosphatase 2C dephosphorylates translation elongation factor 1β and inhibits its PKC‐mediated nucleotide exchange activity in vitro
Author(s) -
Mamoun Choukri Ben,
Goldberg Daniel E.
Publication year - 2001
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2001.02289.x
Subject(s) - biology , elongation factor , phosphorylation , biochemistry , microbiology and biotechnology , protein biosynthesis , phosphatase , ribosome , rna , gene
The elongation step of protein synthesis involves binding of aminoacyl‐tRNA to the ribosomal A site, formation of a peptide bond and translocation of the newly formed peptidyl‐tRNA to the P site. The nucleotide exchange factor EF‐1β plays a major role in the regulation of this process by regenerating a GTP‐bound EF‐1α necessary for each elongation cycle. EF‐1β has been shown to be phosphorylated and its phosphorylation is critical for optimal activity. We have previously identified a serine/threonine protein phosphatase 2C (PP2C) from the human malaria parasite Plasmodium falciparum . In the current work, we performed Far‐Western analysis to identify PfPP2C substrates. Several components of the translation and transcription machinery were identified, including translation elongation factor 1‐beta (PfEF‐1β). PfEF‐1β is efficiently phosphorylated by protein kinase C and this phosphorylation results in a 400% increase in its nucleotide exchange activity. PKC‐phosphorylated PfEF‐1β is readily and selectively dephosphorylated by recombinant and native PfPP2C, which downregulates the nucleotide exchange activity to its basal level. The identification of a translation elongation component as substrate for PP2C suggests an important regulatory function for this enzyme and suggests that it may be a good target for drug design in the fight against malaria.