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

• Autor(a) principal: Erben, Esteban D.
• Data de Publicação: 2010
• Outros Autores: Valguarnera, Ezequiel, Nardelli, Sheila Cristina [UNIFESP], Chung, Janete [UNIFESP], Daum, Sebastian, Potenza, Mariana, Schenkman, Sergio [UNIFESP], Tellez-Inon, Maria T.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000z3hz
• DOI: 10.1016/j.bbamcr.2010.05.006
• Texto Completo: http://dx.doi.org/10.1016/j.bbamcr.2010.05.006; http://repositorio.unifesp.br/handle/11600/32833
• topic: Peptidyl-prolyl cis/trans isomerase; Parvulin; Pin1-type PPIase; Par45

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 Part14. 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. (C) 2010 Elsevier B.V. All rights reserved.