A fish herpesvirus highlights functional diversities among Zα domains related to phase separation induction and A-to-Z conversion
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- Mamadou Amadou Diallo
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Sébastien Pirotte
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Yunlong Hu
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Léa Morvan
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Krzysztof Rakus
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Nicolás M Suárez
- MRC-University of Glasgow Centre for Virus Research , Glasgow G61 1QH, UK
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- Lee PoTsang
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
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- Hisao Saneyoshi
- Department of Medical Sciences, Division of Chemistry, University of Miyazaki , Miyazaki 889-1692, Japan
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- Yan Xu
- Department of Medical Sciences, Division of Chemistry, University of Miyazaki , Miyazaki 889-1692, Japan
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- Andrew J Davison
- MRC-University of Glasgow Centre for Virus Research , Glasgow G61 1QH, UK
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- Peter Tompa
- VIB-VUB Center for Structural Biology, Vrije Universiteit Brussel , Brussel B-1050, Belgium
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- Joel L Sussman
- Department of Chemical and Structural Biology, Weizmann Institute of Science , Rehovot 7610001, Israel
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- Alain Vanderplasschen
- Department of Infectious and Parasitic Diseases, Immunology-Vaccinology, University of Liège , Liège B-4000, Belgium
抄録
<jats:title>Abstract</jats:title> <jats:p>Zalpha (Zα) domains bind to left-handed Z-DNA and Z-RNA. The Zα domain protein family includes cellular (ADAR1, ZBP1 and PKZ) and viral (vaccinia virus E3 and cyprinid herpesvirus 3 (CyHV-3) ORF112) proteins. We studied CyHV-3 ORF112, which contains an intrinsically disordered region and a Zα domain. Genome editing of CyHV-3 indicated that the expression of only the Zα domain of ORF112 was sufficient for normal viral replication in cell culture and virulence in carp. In contrast, its deletion was lethal for the virus. These observations revealed the potential of the CyHV-3 model as a unique platform to compare the exchangeability of Zα domains expressed alone in living cells. Attempts to rescue the ORF112 deletion by a broad spectrum of cellular, viral, and artificial Zα domains showed that only those expressing Z-binding activity, the capacity to induce liquid-liquid phase separation (LLPS), and A-to-Z conversion, could rescue viral replication. For the first time, this study reports the ability of some Zα domains to induce LLPS and supports the biological relevance of dsRNA A-to-Z conversion mediated by Zα domains. This study expands the functional diversity of Zα domains and stimulates new hypotheses concerning the mechanisms of action of proteins containing Zα domains.</jats:p>
収録刊行物
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- Nucleic Acids Research
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Nucleic Acids Research 51 (2), 806-830, 2022-09-22
Oxford University Press (OUP)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360861707157855616
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- ISSN
- 13624962
- 03051048
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- データソース種別
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- Crossref
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