The native structure of the assembled matrix protein 1 of influenza A virus
The native structure of the assembled matrix protein 1 of influenza A virus
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DOI：
10.1038/s41586-020-2696-8
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发表时间：
2020-09-09
期刊：
影响因子：
64.8
通讯作者：
Briggs, John A. G.
中科院分区：
文献类型：
--
作者：
Peukes, Julia;Xiong, Xiaoli;Briggs, John A. G.
甲型流感病毒在每年的流行期间会导致数以百万计的严重病例。流感病毒体中最丰富的蛋白质是基质蛋白 1 (M1)，它通过在病毒膜下形成内骨骼来介导病毒组装 (1)。全长 M1 的结构以及它如何寡聚化以介导病毒粒子的组装尚不清楚。在这里，我们确定了完整病毒颗粒内组装的 M1 的完整结构，以及体外重建的 M1 寡聚物的结构。我们发现 M1 的 C 端结构域在溶液中是无序的，但可以折叠并反式结合到另一个 M1 单体的 N 端结构域，从而将 M1 聚合成线性链，覆盖组装病毒体膜的内表面。在 M1 聚合物中，五个组氨酸残基（由 M1 的三个不同单体贡献）形成一个簇，可以在进入靶细胞后充当 pH 敏感的分解开关。因此，这些结构揭示了流感病毒组装和分解的机制。完整病毒颗粒中甲型流感病毒组装的基质蛋白1的结构以及体外重组的该蛋白质寡聚物的结构揭示了流感病毒组装和分解的机制。
Influenza A virus causes millions of severe cases of disease during annual epidemics. The most abundant protein in influenza virions is matrix protein 1 (M1), which mediates virus assembly by forming an endoskeleton beneath the virus membrane(1). The structure of full-length M1, and how it oligomerizes to mediate the assembly of virions, is unknown. Here we determine the complete structure of assembled M1 within intact virus particles, as well as the structure of M1 oligomers reconstituted in vitro. We find that the C-terminal domain of M1 is disordered in solution but can fold and bind intransto the N-terminal domain of another M1 monomer, thus polymerizing M1 into linear strands that coat the interior surface of the membrane of the assembling virion. In the M1 polymer, five histidine residues-contributed by three different monomers of M1-form a cluster that can serve as the pH-sensitive disassembly switch after entry into a target cell. These structures therefore reveal mechanisms of influenza virus assembly and disassembly.Structures of the assembled matrix protein 1 of influenza A virus in intact virus particles and of oligomers of this protein reconstituted in vitro reveal mechanisms of assembly and disassembly of influenza virus.