Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)
Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)
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DOI：
10.1093/emboj/cdg449
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发表时间：
2003-09-15
期刊：
影响因子：
11.4
通讯作者：
Baudin, F
中科院分区：
文献类型：
--
作者：
Akarsu, H;Burmeister, WP;Baudin, F
在流感病毒感染期间，病毒核糖核蛋白（vRNP）在细胞核中复制，并且在组装成成熟病毒颗粒之前必须输出到细胞质。核输出由细胞蛋白 Crm1 介导，推测由病毒蛋白 NEP/NS2 介导。 NEP 的蛋白水解切割定义了介导 RanGTP 依赖性与 Crm1 结合的 N 端结构域和与病毒基质蛋白 M1 结合的 C 端结构域。 C 端结构域的 2.6 埃晶体结构揭示了两亲性螺旋发夹，其二聚化为四螺旋束。 NEP-M1 相互作用涉及两个关键表位：NEP 上被一簇谷氨酸残基包围的暴露色氨酸 (Trp78)，以及 M1 的基本核定位信号 (NLS)。讨论了 vRNP 导出的影响。
During influenza virus infection, viral ribonucleoproteins (vRNPs) are replicated in the nucleus and must be exported to the cytoplasm before assembling into mature viral particles. Nuclear export is mediated by the cellular protein Crm1 and putatively by the viral protein NEP/NS2. Proteolytic cleavage of NEP defines an N-terminal domain which mediates RanGTP-dependent binding to Crm1 and a C- terminal domain which binds to the viral matrix protein M1. The 2.6 Angstrom crystal structure of the C-terminal domain reveals an amphipathic helical hairpin which dimerizes as a four-helix bundle. The NEP-M1 interaction involves two critical epitopes: an exposed tryptophan (Trp78) surrounded by a cluster of glutamate residues on NEP, and the basic nuclear localization signal (NLS) of M1. Implications for vRNP export are discussed.