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Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses Yu Guo, Wenming Wang, Wei Ji, Maping Deng, Yuna Sun, Honggang Zhou, Cheng Yang, Fei Deng, Hualin Wang, Zhihong Hu, Zhiyong Lou* & Zihe Rao* Crimean-Congo hemorrhagic fever virus (CCHFV), a virus with high mortality in humans, is a member of the genus Nairovirus in the family Bunyaviridae, and is a causative agent of severe hemorrhagic fever (HF). It is classified as a biosafety level 4 pathogen and a potential bioterrorismagent due to its aerosol infectivity and its ability to cause HF outbreaks with high case fatality (~30%). However, little is known about the structural features and function of nucleoproteins (NPs) in the Bunyaviridae, especially in CCHFV. Here we report a 2.3-A resolution crystal structure of the CCHFV nucleoprotein. The protein has a racket-shaped overall structure with distinct "head" and "stalk" domains and differs significantly with NPs reported so far from other negative-sense single-stranded RNA viruses. Furthermore, CCHFV NP shows a distinct metal-dependent DNA-specific endonuclease activity. Single residue mutations in the predicted active site resulted in a significant reduction in the observed endonuclease activity. Our results present a new folding mechanism and function for a negative-strand RNA virus nucleoprotein, extend our structural insight into bunyavirus NPs, and provide a potential target for antiviral drug development to treat CCHFV infection. [ Proc Natl Acad Sci U S A. 2012 Mar 14. doi: 10.1073/pnas.1200808109. Epub ahead of print. PMID: 22421137 ] [ PDF ] |
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A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71 Xiangxi Wang, Wei Peng, Jingshan Ren, Zhongyu Hu, Jiwei Xu, Zhiyong Lou, Xumei Li, Weidong Yin, Xinliang Shen, Claudine Porta, Thomas S Walter, Gwyndaf Evans, Danny Axford, Robin Owen, David J Rowlands, Junzhi Wang*, David I Stuart*, Elizabeth E Fry* & Zihe Rao* Enterovirus 71 1 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 1 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention. [ Nat Struct Mol Biol. 2012 Mar 4. doi: 10.1038/nsmb.2255. Epub ahead of print. PMID: 22388738 ][ PDF ] |
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Crystal structure of the mitochondrial respiratory membrane protein Complex II |
Design of wide spectrum inhibitors targeting the coronavirus main protease (Mpro) |
Crystal structure of the polymerase PA(C)-PB1(N) complex & PA(N) from an avian influenza H5N1 virus |
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Sun F, Huo X, Zhai YJ,
Wang AJ, Xu JX, Su D, Bartlam M & Rao Z*. 2005. Crystal
Structure of Mitochondrial Respiratory Membrane Protein Complex II. Cell,
121: 1043-1057. Links
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