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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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