3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry
3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry
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3.3 — 无包膜病毒的冷冻电镜结构揭示了进入细胞的启动机制
DOI：
10.1016/j.cell.2010.03.041
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发表时间：
2010-04-30
期刊：
影响因子：
64.5
通讯作者：
Zhou, Z. Hong
中科院分区：
文献类型：
--
作者：
Zhang, Xing;Jin, Lei;Zhou, Z. Hong
为了进入细胞，许多无包膜病毒必须从休眠状态转变为引发状态。与包膜病毒的膜融合机制（例如，流感病毒），这种膜穿透机制知之甚少。在这里，使用单粒子冷冻电子显微镜，我们报告了一个3.3埃的结构，引发，感染性亚病毒颗粒的水生呼肠孤病毒。密度图揭示了所有类型氨基酸（甘氨酸除外）的侧链密度，从而能够构建病毒颗粒的全原子模型。我们的结构和生化结果表明，引发涉及的膜穿透蛋白的自裂解，并建议Lys84和Glu76可能有助于这种自裂解在亲核攻击。我们观察到一个肉豆蔻酰基，共价连接到N末端的渗透蛋白和嵌入在一个疏水口袋。这些结果表明，一个精心策划的无包膜病毒进入的过程中，涉及自切割的渗透蛋白暴露之前，其膜插入手指。
To achieve cell entry, many nonenveloped viruses must transform from a dormant to a primed state. In contrast to the membrane fusion mechanism of enveloped viruses (e.g., influenza virus), this membrane penetration mechanism is poorly understood. Here, using single-particle cryo-electron microscopy, we report a 3.3 angstrom structure of the primed, infectious subvirion particle of aquareovirus. The density map reveals side-chain densities of all types of amino acids (except glycine), enabling construction of a full-atom model of the viral particle. Our structure and biochemical results show that priming involves autocleavage of the membrane penetration protein and suggest that Lys84 and Glu76 may facilitate this autocleavage in a nucleophilic attack. We observe a myristoyl group, covalently linked to the N terminus of the penetration protein and embedded in a hydrophobic pocket. These results suggest a well-orchestrated process of nonenveloped virus entry involving autocleavage of the penetration protein prior to exposure of its membrane-insertion finger.