Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids

Esteban D. Erben, Ezequiel Valguarnera, Sheila Nardelli, Janete Chung, Sebastian Daum, Mariana Potenza, Sergio Schenkman, María T. Téllez-Iñón

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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: kcat/KM=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.

Original languageEnglish
Pages (from-to)1028-1037
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1803
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Par45
  • Parvulin
  • Peptidyl-prolyl cis/trans isomerase
  • Pin1-type PPIase

Fingerprint

Dive into the research topics of 'Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids'. Together they form a unique fingerprint.

Cite this