Akarsu Hatice, Burmeister Wilhelm P, Petosa Carlo, Petit Isabelle, Müller Christoph W, Ruigrok Rob W H, Baudin Florence
EMBL Grenoble Outstation, BP 181, 38042 Grenoble cedex 9, France.
EMBO J. 2003 Sep 15;22(18):4646-55. doi: 10.1093/emboj/cdg449.
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 A 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.
在流感病毒感染过程中，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转运至细胞质。核输出由细胞蛋白Crm1介导，推测也由病毒蛋白NEP/NS2介导。NEP的蛋白水解切割产生一个N端结构域，该结构域介导与Crm1的RanGTP依赖性结合，以及一个与病毒基质蛋白M1结合的C端结构域。C端结构域的2.6埃晶体结构揭示了一个两亲性螺旋发夹结构，该结构以四螺旋束的形式二聚化。NEP-M1相互作用涉及两个关键表位：NEP上一个被谷氨酸残基簇包围的暴露色氨酸（Trp78），以及M1的碱性核定位信号（NLS）。文中讨论了其对vRNP输出的影响。
