An atypical Peptidil-Prolyl Cis/Trans isomerase is required for Trypanosoma brucei cell proliferation”.

ERBEN E.D., NARDELLI S., VALGUARNERA E., CHUNG J., SCHENKMAN S., TÉLLEZ-IÑÓN M.T

Buzios, Brasil

Congreso; XIII International Congress of Protistology. XXXVI Annual Meeting on Basic Chagas Disease. XXV Annual Meeting of the Brazilian Society of Protozoology.; 2009

Soc Parasitologia

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} a:link, span.MsoHyperlink {color:blue; text-decoration:underline; text-underline:single;} a:visited, span.MsoHyperlinkFollowed {color:purple; text-decoration:underline; text-underline:single;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> The parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases) catalyzes the cis/trans isomerization of the peptide bonds preceding Pro residues and it has been suggested they play a critical role controlling cell-cycle progression. A novel member of the parvulin family of PPIases named Par45 was identified in the TriTryp genome. Analysis of the sequence of Par45 showed the existence of the sequence motifs typical of the parvulin catalytic core. Like most other parvulins, Par45 has an N-terminal extension but in contrast to hPin1, Par45 contains a FHA instead a WW domain at N-terminal end. A comparison of the relative values of the specificity constants for various substrates shows a general pattern as it was found for Par14 with 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). In contrast to Pin1 but like Par14, Par45 does not accelerate the cis/trans interconversion of acidic substrates containing Glu-Pro bonds. By using a proteomic approach and YTH analysis we found that Par45 associate with proteins involved in transcription and/or RNA processing. Immunolocalization of Par45 corroborates the presence of the parvulin within the nuclei of parasites. Single RNA interference (RNAi)-mediated knock-down of Par45 suggest lethality and thus a required function shared by others Pin1-type PPIases. These findings coupled with the other results suggest that Par45 is linked to the RNA processing machinery and is necessary for normal cell proliferation in T. brucei. Supported by FONCYT, CONICET, Prosul- CNPq, and FAPES