Cargando…

Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii

We had shown in our previous study that TgUrm1 (ubiquitin-related Modifier 1) was involved in the regulation of anti-oxidant stress in Toxoplasma gondii by conjugating with TgAhp1. It is generally believed that Urm1 binds to target proteins through a mechanism involving Uba (ubiquitin-like activator...

Descripción completa

Detalles Bibliográficos
Autores principales: Xiao, Qianqian, Li, Jinxuan, Chen, Junpeng, Tan, Qianqian, Chen, Xiao, Li, Hongmei, Zhao, Xiaomin, Zhang, Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499322/
https://www.ncbi.nlm.nih.gov/pubmed/36142209
http://dx.doi.org/10.3390/ijms231810298
_version_ 1784794968848596992
author Xiao, Qianqian
Li, Jinxuan
Chen, Junpeng
Tan, Qianqian
Chen, Xiao
Li, Hongmei
Zhao, Xiaomin
Zhang, Xiao
author_facet Xiao, Qianqian
Li, Jinxuan
Chen, Junpeng
Tan, Qianqian
Chen, Xiao
Li, Hongmei
Zhao, Xiaomin
Zhang, Xiao
author_sort Xiao, Qianqian
collection PubMed
description We had shown in our previous study that TgUrm1 (ubiquitin-related Modifier 1) was involved in the regulation of anti-oxidant stress in Toxoplasma gondii by conjugating with TgAhp1. It is generally believed that Urm1 binds to target proteins through a mechanism involving Uba (ubiquitin-like activator protein). Here, we identified the TgUrm1-exclusive ubiquitin-like activator-TgUba1, which was located in the cytoplasm of Toxoplasma. TgUba1 contained three domains, including the atrophin-1 domain (ANT1), the E1-like domain (AD), and the rhodanese homology domain (RHD). We explored the interaction of TgUba1 with TgUrm1, and the AD domain was essential for the interaction of the two proteins. The TgUba1 knockout and complementary mutants were obtained based on CRISPR/Cas9 gene editing technology. The knockout of TgUba1 attenuated parasite proliferation and virulence in mice, but not invasion and egress processes, revealing the pivotal role played by TgUba1 in T. gondii survival. Meanwhile, the conjugate band of TgUrm1 was significantly reduced under oxidative stress stimulation without TgUba1, indicating that TgUba1 enhanced the targeted conjugation ability of TgUrm1 in response to oxidative stress, especially under diamide (Dia) stimulation. Furthermore, eleven TgUba1-interacting proteins were identified by proximity-based protein labeling techniques, relating them to ubiquitin-like modifications, anti-oxidative stress and metabolic regulation processes. In conclusion, TgUba1 was essential for T. gondii survival and might be a potential ubiquitin-like activator protein for TgUrm1.
format Online
Article
Text
id pubmed-9499322
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94993222022-09-23 Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii Xiao, Qianqian Li, Jinxuan Chen, Junpeng Tan, Qianqian Chen, Xiao Li, Hongmei Zhao, Xiaomin Zhang, Xiao Int J Mol Sci Article We had shown in our previous study that TgUrm1 (ubiquitin-related Modifier 1) was involved in the regulation of anti-oxidant stress in Toxoplasma gondii by conjugating with TgAhp1. It is generally believed that Urm1 binds to target proteins through a mechanism involving Uba (ubiquitin-like activator protein). Here, we identified the TgUrm1-exclusive ubiquitin-like activator-TgUba1, which was located in the cytoplasm of Toxoplasma. TgUba1 contained three domains, including the atrophin-1 domain (ANT1), the E1-like domain (AD), and the rhodanese homology domain (RHD). We explored the interaction of TgUba1 with TgUrm1, and the AD domain was essential for the interaction of the two proteins. The TgUba1 knockout and complementary mutants were obtained based on CRISPR/Cas9 gene editing technology. The knockout of TgUba1 attenuated parasite proliferation and virulence in mice, but not invasion and egress processes, revealing the pivotal role played by TgUba1 in T. gondii survival. Meanwhile, the conjugate band of TgUrm1 was significantly reduced under oxidative stress stimulation without TgUba1, indicating that TgUba1 enhanced the targeted conjugation ability of TgUrm1 in response to oxidative stress, especially under diamide (Dia) stimulation. Furthermore, eleven TgUba1-interacting proteins were identified by proximity-based protein labeling techniques, relating them to ubiquitin-like modifications, anti-oxidative stress and metabolic regulation processes. In conclusion, TgUba1 was essential for T. gondii survival and might be a potential ubiquitin-like activator protein for TgUrm1. MDPI 2022-09-07 /pmc/articles/PMC9499322/ /pubmed/36142209 http://dx.doi.org/10.3390/ijms231810298 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiao, Qianqian
Li, Jinxuan
Chen, Junpeng
Tan, Qianqian
Chen, Xiao
Li, Hongmei
Zhao, Xiaomin
Zhang, Xiao
Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title_full Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title_fullStr Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title_full_unstemmed Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title_short Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii
title_sort uba1: a potential ubiquitin-like activator protein of urm1 in toxoplasma gondii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499322/
https://www.ncbi.nlm.nih.gov/pubmed/36142209
http://dx.doi.org/10.3390/ijms231810298
work_keys_str_mv AT xiaoqianqian uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT lijinxuan uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT chenjunpeng uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT tanqianqian uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT chenxiao uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT lihongmei uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT zhaoxiaomin uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii
AT zhangxiao uba1apotentialubiquitinlikeactivatorproteinofurm1intoxoplasmagondii