Sarita Aryal1
National Tsinghua University, Hsinchu 300, Taiwan
Title: Structural basis of investigation of cyclophilin 1 and cyclophilin 2 with Myb 3 transcription factor in Trichomonas veginalis
Biography
Biography: Sarita Aryal1
Abstract
Trichomoniasis, caused by Trichomonas vaginalis is the most common non-viral sexually transmitted disease in humans and is correlated with elevated susceptibility to HIV and HPV transmission. During pregnancy overload of iron can express hydrogenosomal enzymes and help in cytoadherence of T. vaginalis for its growth. Previous studies suggested that ap65-1 gene is involving in parasitic cytoadherence and its transcription is mediated by the coordinated action of Myb1, Myb2, and Myb3 transcription factors. Cyclophilin 1 (TvCyP1) and Cyclophilin 2 (TvCyP2), are peptidyl-prolyl isomerase present in the human parasite Trichomonas vaginalis, interacts with Myb transcription factors. In this study, we determined the unique structure of TvCyP2 as a monomer where its extra N-terminus loop goes in to the catalytic pocket of its own monomer fitting well into the active site and auxiliary pocket, respectively. Surprisingly N-terminus loop is mimicking the substrate as cyclosporine or Myb1 peptide which showed to have auto inhibition mechanism for TvCyP2. Using NMR and other techniques, we are now trying to find the role of this extra N-terminus extension on enzyme catalytic activity and auto inhibition. For the protein-protein interactions, our NMR data further showed that TvCyP1 and TvCyP2 both have interaction with minimum TvCyP1-binding sequence of Myb3 (Myb3 50–87). This result is further confirmed using ITC which also showed this myb3 peptide does bind with TvCyP1 and TvCyP2.Together with the finding we are further focusing on X-Ray studies for the complex structures TvCyP1 and TvCyP2 with Myb3 peptide. Together, the structure of TvCyP2 and detailed structural insights on TvCyP1-Myb3 interaction could pave the way for newer drugs to treat drug resistant strains.