N-Terminal Segment of <i>Tv</i>CyP2 Cyclophilin from <i>Trichomonas vaginalis</i> Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization

• Main Authors: Sarita Aryal, Hong-Ming Hsu, Yuan-Chao Lou, Chien-Hsin Chu, Jung-Hsiang Tai, Chun-Hua Hsu, Chinpan Chen
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Biomolecules
• Subjects: Cyclophilin; cytoadherence; peptidyl-prolyl isomerase; protein trafficking; <i>Trichomonas vaginalis</i>; trichomoniasis
• Online Access: https://www.mdpi.com/2218-273X/10/9/1239

In <i>Trichomonas vaginalis </i>(<i>T. vaginalis</i>), cyclophilins play a vital role in dislodging Myb proteins from the membrane compartment and leading them to nuclear translocation. We previously reported that <i>Tv</i>CyP1 cyclophilin from <i>T. vaginalis</i> forms a dimer and plays an essential role in moving the Myb1 transcription factor toward the nucleus. In comparison, <i>Tv</i>CyP2 containing an extended segment at the N-terminus (N-terminal segment) formed a monomer and showed a different role in regulating protein trafficking. Four X-ray structures of <i>Tv</i>CyP2 were determined under various conditions, all showing the N-terminal segment interacting with the active site of a neighboring <i>Tv</i>CyP2, an unusual interaction. NMR study revealed that this particular interaction exists in solution as well and also the N-terminal segment seems to interact with the membrane. In vivo study of <i>Tv</i>CyP2 and <i>Tv</i>CyP2-∆N (<i>Tv</i>CyP2 without the N-terminal segment) indicated that both proteins have different subcellular localization. Together, the structural and functional characteristics at the N-terminal segment offer valuable information for insights into the mechanism of how <i>Tv</i>CyP2 regulates protein trafficking, which may be applied in drug development to prevent pathogenesis and disease progression in<i> T. vaginalis </i>infection.