Cargando…

N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization

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 tr...

Descripción completa

Detalles Bibliográficos
Autores principales: Aryal, Sarita, Hsu, Hong-Ming, Lou, Yuan-Chao, Chu, Chien-Hsin, Tai, Jung-Hsiang, Hsu, Chun-Hua, Chen, Chinpan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563477/
https://www.ncbi.nlm.nih.gov/pubmed/32859063
http://dx.doi.org/10.3390/biom10091239
_version_ 1783595498066673664
author Aryal, Sarita
Hsu, Hong-Ming
Lou, Yuan-Chao
Chu, Chien-Hsin
Tai, Jung-Hsiang
Hsu, Chun-Hua
Chen, Chinpan
author_facet Aryal, Sarita
Hsu, Hong-Ming
Lou, Yuan-Chao
Chu, Chien-Hsin
Tai, Jung-Hsiang
Hsu, Chun-Hua
Chen, Chinpan
author_sort Aryal, Sarita
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7563477
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75634772020-10-27 N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization Aryal, Sarita Hsu, Hong-Ming Lou, Yuan-Chao Chu, Chien-Hsin Tai, Jung-Hsiang Hsu, Chun-Hua Chen, Chinpan Biomolecules Article 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. MDPI 2020-08-26 /pmc/articles/PMC7563477/ /pubmed/32859063 http://dx.doi.org/10.3390/biom10091239 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aryal, Sarita
Hsu, Hong-Ming
Lou, Yuan-Chao
Chu, Chien-Hsin
Tai, Jung-Hsiang
Hsu, Chun-Hua
Chen, Chinpan
N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title_full N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title_fullStr N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title_full_unstemmed N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title_short N-Terminal Segment of TvCyP2 Cyclophilin from Trichomonas vaginalis Is Involved in Self-Association, Membrane Interaction, and Subcellular Localization
title_sort n-terminal segment of tvcyp2 cyclophilin from trichomonas vaginalis is involved in self-association, membrane interaction, and subcellular localization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563477/
https://www.ncbi.nlm.nih.gov/pubmed/32859063
http://dx.doi.org/10.3390/biom10091239
work_keys_str_mv AT aryalsarita nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT hsuhongming nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT louyuanchao nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT chuchienhsin nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT taijunghsiang nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT hsuchunhua nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization
AT chenchinpan nterminalsegmentoftvcyp2cyclophilinfromtrichomonasvaginalisisinvolvedinselfassociationmembraneinteractionandsubcellularlocalization