Structural basis of membrane budding by the nuclear egress complex of herpesviruses
Structural basis of membrane budding by the nuclear egress complex of herpesviruses
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DOI：
10.15252/embj.201592359
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发表时间：
2015-12-02
期刊：
影响因子：
11.4
通讯作者：
Heldwein, Ekaterina E.
中科院分区：
文献类型：
--
作者：
Bigalke, Janna M.;Heldwein, Ekaterina E.
在核出口过程中，疱疹病毒衣壳在内核膜上出芽，形成核周病毒颗粒，随后与外核膜融合，将衣壳释放到细胞质中。这种不寻常的出芽过程是由两种保守的病毒蛋白UL31和UL34组成的核出口复合物（NEC）介导的。早些时候，我们发现疱疹病毒核出口复合物（NEC）可以在体外出芽合成膜，而无需其他蛋白质的帮助，通过在出芽膜内形成涂层状六边形支架。为了了解NEC介导的膜出芽的结构基础，我们确定了两种疱疹病毒NEC的晶体结构。NEC晶体中观察到的六方晶格概括了出芽囊泡内的蜂窝状涂层。通过诱变的寡聚物界面的扰动在体外阻断出芽，证实NEC寡聚成蜂窝晶格驱动出芽。该结构代表了由膜变形蛋白形成的寡聚体阵列的第一个原子水平视图，使得解剖其独特的出芽机制和设计抑制剂来阻止它成为可能。
During nuclear egress, herpesvirus capsids bud at the inner nuclear membrane forming perinuclear viral particles that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytoplasm. This unusual budding process is mediated by the nuclear egress complex (NEC) composed of two conserved viral proteins, UL31 and UL34. Earlier, we discovered that the herpesvirus nuclear egress complex (NEC) could bud synthetic membranes in vitro without the help of other proteins by forming a coat-like hexagonal scaffold inside the budding membrane. To understand the structural basis of NEC-mediated membrane budding, we determined the crystal structures of the NEC from two herpesviruses. The hexagonal lattice observed in the NEC crystals recapitulates the honeycomb coats within the budded vesicles. Perturbation of the oligomeric interfaces through mutagenesis blocks budding in vitro confirming that NEC oligomerization into a honeycomb lattice drives budding. The structure represents the first atomic-level view of an oligomeric array formed by a membrane-deforming protein, making possible the dissection of its unique budding mechanism and the design of inhibitors to block it.