气候变化领域集成服务门户(CCPortal): Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry

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DOI	10.1073/pnas.2107408118
	Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry
	Khare B.; Klose T.; Fang Q.; Rossmann M.G.; Kuhn R.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:34
英文摘要	Usutu virus (USUV) is an emerging arbovirus in Europe that has been increasingly identified in asymptomatic humans and donated blood samples and is a cause of increased incidents of neuroinvasive human disease. Treatment or prevention options for USUV disease are currently nonexistent, the result of a lack of understanding of the fundamental elements of USUV pathogenesis. Here, we report two structures of the mature USUV virus, determined at a resolution of 2.4 Å, using single-particle cryogenic electron microscopy. Mature USUV is an icosahedral shell of 180 copies of envelope (E) and membrane (M) proteins arranged in the classic herringbone pattern. However, unlike previous reports of flavivirus structures, we observe virus subpopulations and differences in the fusion loop disulfide bond. Presence of a second, unique E glycosylation site could elucidate host interactions, contributing to the broad USUV tissue tropism. The structures provide a basis for exploring USUV interactions with glycosaminoglycans and lectins, the role of the RGD motif as a receptor, and the inability of West Nile virus therapeutic antibody E16 to neutralize the mature USUV strain SAAR-1776. Finally, we identify three lipid binding sites and predict key residues that likely participate in virus stability and flexibility during membrane fusion. Our findings provide a framework for the development of USUV therapeutics and expand the current knowledge base of flavivirus biology. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cryo-electron microscopy; Flavivirus; Single-particle analysis; Usutu virus
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/238821
作者单位	Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, United States
推荐引用方式 GB/T 7714	Khare B.,Klose T.,Fang Q.,et al. Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry[J],2021,118(34).
APA	Khare B.,Klose T.,Fang Q.,Rossmann M.G.,&Kuhn R.J..(2021).Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry.Proceedings of the National Academy of Sciences of the United States of America,118(34).
MLA	Khare B.,et al."Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry".Proceedings of the National Academy of Sciences of the United States of America 118.34(2021).