Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids.
The parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases) catalyzes the cis/trans isomerization of the peptide bonds preceding Pro residues. Eukaryotic parvulin-type PPIases have been shown to be involved in cell proliferation and cell cycle progression. Here we present the biochemical and molecular characterization of a novel multi-domain parvulin-type PPIase from the human pathogenic Trypanosoma cruzi, annotated as TcPar45. Like most other parvulins, Par45 has an N-terminal extension, but, in contrast to human Pin1, it contains a forkhead-associated domain (FHA) instead of a WW domain at the N-terminal end. Par45 shows a strong preference for a substrate with the basic Arg residue preceding Pro (Suc-Ala-Arg-Pro-Phe-NH-Np: k(cat)/K(M)=97.1 /M/s), like that found for human Par14. In contrast to human Pin1, but similarly to Par14, Par45 does not accelerate the cis/trans interconversion of acidic substrates containing Glu-Pro bonds. It is preferentially located in the parasite nucleus. Single RNA interference (RNAi)-mediated knock-down showed that there was a growth inhibition in procyclic Trypanosoma brucei cells. These results identify Par45 as a phosphorylation-independent parvulin required for normal cell proliferation in a unicellular eukaryotic cell.
Erben
Esteban D
ED
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET) Buenos Aires, R. Argentina.
Valguarnera
Ezequiel
E
Nardelli
Sheila
S
Chung
Janete
J
Daum
Sebastian
S
Potenza
Mariana
M
Schenkman
Sergio
S
Téllez-Iñón
María T
MT
D000595:Amino Acid Sequence; D000818:Animals; D002457:Cell Extracts / Q000737:chemistry; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection; D014351:Trypanosomatina / Q000235:genetics*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
D002457:Cell Extracts; D019696:Peptidylprolyl Isomerase