TY - JOUR
T1 - Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids
AU - Erben, Esteban D.
AU - Valguarnera, Ezequiel
AU - Nardelli, Sheila
AU - Chung, Janete
AU - Daum, Sebastian
AU - Potenza, Mariana
AU - Schenkman, Sergio
AU - Téllez-Iñón, María T.
N1 - Funding Information:
We thank Prof. Dr. Gunter Fischer and Dr. Cordelia Schiene-Fischer for their assistance, G. Prat Gay and A. Heer for the Maldi analysis. E. E. thanks the DAAD for a fellowship with the student exchange program. The work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, Argentina). Part of this work was supported by grants from Prosul-CNPq and FAPESP (Brazil).
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Par45
KW - Parvulin
KW - Peptidyl-prolyl cis/trans isomerase
KW - Pin1-type PPIase
UR - http://www.scopus.com/inward/record.url?scp=77954952486&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2010.05.006
DO - 10.1016/j.bbamcr.2010.05.006
M3 - Article
C2 - 20580912
AN - SCOPUS:77954952486
SN - 0167-4889
VL - 1803
SP - 1028
EP - 1037
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 9
ER -