气候变化领域集成服务门户(CCPortal): Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2

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DOI	10.1073/pnas.2020587118
	Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2
	Pei J.; Wagner N.D.; Zou A.J.; Chatterjee S.; Borek D.; Cole A.R.; Kim P.J.; Basler C.F.; Otwinowski Z.; Gross M.L.; Amarasinghe G.K.; Leung D.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Human respiratory syncytial virus (RSV) nonstructural protein 2 (NS2) inhibits host interferon (IFN) responses stimulated by RSV infection by targeting early steps in the IFN-signaling pathway. But the molecular mechanisms related to how NS2 regulates these processes remain incompletely understood. To address this gap, here we solved the X-ray crystal structure of NS2. This structure revealed a unique fold that is distinct from other known viral IFN antagonists, including RSV NS1. We also show that NS2 directly interacts with an inactive conformation of the RIG-I–like receptors (RLRs) RIG-I and MDA5. NS2 binding prevents RLR ubiquitination, a process critical for prolonged activation of downstream signaling. Structural analysis, including by hydrogen-deuterium exchange coupled to mass spectrometry, revealed that the N terminus of NS2 is essential for binding to the RIG-I caspase activation and recruitment domains. N-terminal mutations significantly diminish RIG-I interactions and result in increased IFNβ messenger RNA levels. Collectively, our studies uncover a previously unappreciated regulatory mechanism by which NS2 further modulates host responses and define an approach for targeting host responses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	IFN antagonist; Nonstructural protein; NS2; RSV
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180355
作者单位	John T. Milliken Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Chemistry, Washington University in St. Louis, St. Louis, MO 63110, United States; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, United States
推荐引用方式 GB/T 7714	Pei J.,Wagner N.D.,Zou A.J.,et al. Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2[J],2021,118(10).
APA	Pei J..,Wagner N.D..,Zou A.J..,Chatterjee S..,Borek D..,...&Leung D.W..(2021).Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Pei J.,et al."Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).