Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression.
Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression.
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马尔堡病毒 VP40 的晶体结构揭示了基质组装的广泛基本补丁以及免疫抑制所需的 N 端结构域。
DOI：
10.1128/jvi.01597-15
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发表时间：
2016
影响因子：
5.4
通讯作者：
Saphire,EricaOllmann
中科院分区：
文献类型：
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作者：
Oda,Shun-Ichiro;Noda,Takeshi;Wijesinghe,KaveeshaJ;Halfmann,Peter;Bornholdt,ZacharyA;Abelson,DafnaM;Armbrust,Tammy;Stahelin,RobertV;Kawaoka,Yoshihiro;Saphire,EricaOllmann
马尔堡病毒（MARV）是丝状病毒家族的一员，可引起严重的出血热，致死率高达90%。MARV基质蛋白VP 40对于新复制病毒的组装和释放至关重要，并且还抑制感染细胞中的免疫信号传导。本文报道了MARV VP 40的晶体结构。我们发现MARV VP 40在溶液中形成二聚体，由N-末端结构域介导，并且这种二聚体的形成对于病毒样颗粒的出芽是必不可少的。我们还发现N-末端结构域对于免疫拮抗作用是必要和充分的。MARV VP 40的C-末端结构域是免疫抑制所必需的，但也是病毒组装所必需的。埃博拉病毒的C-末端结构域与埃博拉病毒的C-末端结构域只有16%的相同性，在结构上与埃博拉病毒的C-末端结构域不同，并形成一个明显的宽而平的阳离子表面，在病毒组装过程中可能与细胞膜相互作用。重要信息马尔堡病毒是埃博拉病毒的表亲，可引起严重的出血热，在最近的疫情中可观察到高达90%的致死率。马尔堡病毒蛋白质的分子结构和可视化图像对于抗病毒药物的开发至关重要。马尔堡病毒生命周期中的一个关键蛋白是VP 40，它既组装病毒又抑制免疫系统。在这里，我们提供了马尔堡病毒VP 40的分子结构，说明了与埃博拉病毒VP 40的差异，并揭示了马尔堡VP 40组装后代和抑制免疫功能的表面。
Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly.IMPORTANCEMarburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever, with up to 90% lethality seen in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential for the development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Here we provide the molecular structure of Marburg virus VP40, illustrate differences from VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function.