N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
Journal
Biomolecules
Journal Volume
10
Journal Issue
9
Date Issued
2020
Author(s)
Abstract
In Trichomonas vaginalis (T. vaginalis), cyclophilins play a vital role in dislodging Myb proteins from the membrane compartment and leading them to nuclear translocation. We previously reported that TvCyP1 cyclophilin from T. vaginalis forms a dimer and plays an essential role in moving the Myb1 transcription factor toward the nucleus. In comparison, TvCyP2 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 TvCyP2 were determined under various conditions, all showing the N-terminal segment interacting with the active site of a neighboring TvCyP2, 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 TvCyP2 and TvCyP2-∆N (TvCyP2 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 TvCyP2 regulates protein trafficking, which may be applied in drug development to prevent pathogenesis and disease progression in T. vaginalis infection.
Subjects
Cyclophilin; Trichomonas vaginalis; cytoadherence; peptidyl-prolyl isomerase; protein trafficking; trichomoniasis
Other Subjects
cyclophilin; dodecyl sulfate sodium; transcription factor; cyclophilin; peptide fragment; protozoal protein; recombinant protein; amino terminal sequence; Article; binding affinity; cellular distribution; circular dichroism; comparative study; controlled study; crystal structure; crystallization; crystallography; disease exacerbation; drug structure; enzyme activity; enzyme localization; Escherichia coli; flow rate; helical structure; heteronuclear single quantum coherence; high performance liquid chromatography; immunoprecipitation; isomerization; light scattering; melting point; melting temperature; membrane interaction; molecular weight; multiangle angle static light scattering; nonhuman; nuclear magnetic resonance spectroscopy; pH measurement; plasmid; polyacrylamide gel electrophoresis; protein conformation; protein expression; protein interaction; protein secondary structure; protein structure; protein synthesis; protein tertiary structure; proton nuclear magnetic resonance; risk factor; sequence alignment; size exclusion chromatography; steady state; structure analysis; surface structure; Trichomonas vaginalis; trichomoniasis; Western blotting; X ray crystallography; X ray diffraction; alpha helix; amino acid sequence; binding site; chemistry; endoplasmic reticulum; genetics; human; metabolism; molecular model; nucleocytoplasmic transport; protein domain; protein stability; protein transport; sequence homology; Trichomonas vaginalis; Active Transport, Cell Nucleus; Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; Cyclophilins; Endoplasmic Reticulum; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Peptide Fragments; Protein Conformation, alpha-Helical; Protein Interaction Domains and Motifs; Protein Stability; Protein Transport; Protozoan Proteins; Recombinant Proteins; Sequence Homology, Amino Acid; Transcription Factors; Trichomonas vaginalis
Publisher
MDPI
Type
journal article