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Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish
Teleost type I interferons (IFNs) are categorized into group I and II subgroups that bind to distinct receptors to activate antiviral responses. However, the interaction between ifn ligands and receptors has not fully been understood. In this study, the crystal structure of grass carp [Ctenopharyngo...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980424/ https://www.ncbi.nlm.nih.gov/pubmed/35392096 http://dx.doi.org/10.3389/fimmu.2022.862764 |
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author | Wang, Zixuan Xu, Jing Feng, Jianhua Wu, Kaizheng Chen, Kangyong Jia, Zhao Zhu, Xiaozhen Huang, Wenji Zhao, Xin Liu, Qin Wang, Bangjie Chen, Xinhua Wang, Junya Zou, Jun |
author_facet | Wang, Zixuan Xu, Jing Feng, Jianhua Wu, Kaizheng Chen, Kangyong Jia, Zhao Zhu, Xiaozhen Huang, Wenji Zhao, Xin Liu, Qin Wang, Bangjie Chen, Xinhua Wang, Junya Zou, Jun |
author_sort | Wang, Zixuan |
collection | PubMed |
description | Teleost type I interferons (IFNs) are categorized into group I and II subgroups that bind to distinct receptors to activate antiviral responses. However, the interaction between ifn ligands and receptors has not fully been understood. In this study, the crystal structure of grass carp [Ctenopharyngodon idella (Ci)] IFNa has been solved at 1.58Å and consists of six helices. The CiIFNa displays a typical structure of type I IFNs with a straight helix F and lacks a helix element in the AB loop. Superposition modeling identified several key residues involved in the interaction with receptors. It was found that CiIFNa bound to cytokine receptor family B (CRFB) 1, CRFB2, and CRFB5, and the three receptors could form heterodimeric receptor complexes. Furthermore, mutation of Leu27, Glu103, Lys117, and His165 markedly decreased the phosphorylation of signal transducer and activator of transcription (STAT) 1a induced by CiIFNa in the Epithelioma papulosum cyprini (EPC) cells, and Glu103 was shown to be required for the CiIFNa-activated antiviral activity. Interestingly, wild-type and mutant CiIFNa proteins did not alter the phosphorylation levels of STAT1b. Our results demonstrate that fish type I IFNs, although structurally conserved, interact with the receptors in a manner that may differ from mammalian homologs. |
format | Online Article Text |
id | pubmed-8980424 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89804242022-04-06 Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish Wang, Zixuan Xu, Jing Feng, Jianhua Wu, Kaizheng Chen, Kangyong Jia, Zhao Zhu, Xiaozhen Huang, Wenji Zhao, Xin Liu, Qin Wang, Bangjie Chen, Xinhua Wang, Junya Zou, Jun Front Immunol Immunology Teleost type I interferons (IFNs) are categorized into group I and II subgroups that bind to distinct receptors to activate antiviral responses. However, the interaction between ifn ligands and receptors has not fully been understood. In this study, the crystal structure of grass carp [Ctenopharyngodon idella (Ci)] IFNa has been solved at 1.58Å and consists of six helices. The CiIFNa displays a typical structure of type I IFNs with a straight helix F and lacks a helix element in the AB loop. Superposition modeling identified several key residues involved in the interaction with receptors. It was found that CiIFNa bound to cytokine receptor family B (CRFB) 1, CRFB2, and CRFB5, and the three receptors could form heterodimeric receptor complexes. Furthermore, mutation of Leu27, Glu103, Lys117, and His165 markedly decreased the phosphorylation of signal transducer and activator of transcription (STAT) 1a induced by CiIFNa in the Epithelioma papulosum cyprini (EPC) cells, and Glu103 was shown to be required for the CiIFNa-activated antiviral activity. Interestingly, wild-type and mutant CiIFNa proteins did not alter the phosphorylation levels of STAT1b. Our results demonstrate that fish type I IFNs, although structurally conserved, interact with the receptors in a manner that may differ from mammalian homologs. Frontiers Media S.A. 2022-03-22 /pmc/articles/PMC8980424/ /pubmed/35392096 http://dx.doi.org/10.3389/fimmu.2022.862764 Text en Copyright © 2022 Wang, Xu, Feng, Wu, Chen, Jia, Zhu, Huang, Zhao, Liu, Wang, Chen, Wang and Zou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wang, Zixuan Xu, Jing Feng, Jianhua Wu, Kaizheng Chen, Kangyong Jia, Zhao Zhu, Xiaozhen Huang, Wenji Zhao, Xin Liu, Qin Wang, Bangjie Chen, Xinhua Wang, Junya Zou, Jun Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title | Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title_full | Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title_fullStr | Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title_full_unstemmed | Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title_short | Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish |
title_sort | structural and functional analyses of type i ifna shed light into its interaction with multiple receptors in fish |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980424/ https://www.ncbi.nlm.nih.gov/pubmed/35392096 http://dx.doi.org/10.3389/fimmu.2022.862764 |
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