Structural basis for Epstein-Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins.
Structural basis for Epstein-Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins.
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由GP42和GHGL进入糖蛋白介导的Epstein-Barr病毒宿主细胞托管的结构基础。
DOI：
10.1038/ncomms13557
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发表时间：
2016-12-08
影响因子：
16.6
通讯作者：
Jardetzky, Theodore S.
中科院分区：
文献类型：
--
作者：
Sathiyamoorthy, Karthik;Hu, Yao Xiong;Mohl, Britta S.;Chen, Jia;Longnecker, Richard;Jardetzky, Theodore S.
Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins.尽管它们在宿主细胞向性和相关疾病病理学中很重要，但这些病毒糖蛋白之间潜在的和重要的相互作用仍然知之甚少。对于 Epstein-Barr 病毒 (EBV)，gHgL/gp42 复合物结合 HLA II 类以激活与 B 细胞的膜融合，但 gp42 抑制融合和进入上皮细胞。为了阐明 gp42 控制 EBV 感染的细胞特异性的机制，我们确定了与抗 gHgL 抗体 (E1D1) 结合的 gHgL/gp42 复合物的结构。 EBV 趋向性的关键调节因子是 gp42 N 端结构域，它通过包裹三个 gH 结构域的外部将 HLA 结合结构域与 gHgL 相连。 gp42 N 末端结构域和 E1D1 均选择性抑制上皮细胞融合；然而，它们与 gHgL 的不同表面结合。这些观察结果阐明了 EBV 宿主细胞趋向性的关键决定因素。 疱疹病毒（例如 Epstein-Barr 病毒）进入宿主细胞是由多种糖蛋白介导的。在这里，作者展示了与抗 gHgL 抗体结合的病毒糖蛋白复合物 gHgL/gp42 的结构，阐明了 EBV 宿主细胞向性的决定因素。
Herpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. For Epstein–Barr virus (EBV), gHgL/gp42 complexes bind HLA class II to activate membrane fusion with B cells, but gp42 inhibits fusion and entry into epithelial cells. To clarify the mechanism by which gp42 controls the cell specificity of EBV infection, here we determined the structure of gHgL/gp42 complex bound to an anti-gHgL antibody (E1D1). The critical regulator of EBV tropism is the gp42 N-terminal domain, which tethers the HLA-binding domain to gHgL by wrapping around the exterior of three gH domains. Both the gp42 N-terminal domain and E1D1 selectively inhibit epithelial-cell fusion; however, they engage distinct surfaces of gHgL. These observations clarify key determinants of EBV host cell tropism. The entry of herpesviruses (such as Epstein-Barr virus) into host cells is mediated by a multitude of glycoproteins. Here, the authors show the structure of a viral glycoprotein complex, gHgL/gp42, bound to an anti-gHgL antibody, clarifying determinants of EBV host cell tropism.
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DOI：
10.1107/s0907444910051218
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Bunkóczi G;Read RJ
通讯作者：
Read RJ
影响因子：
3.1
作者：
Hutt-Fletcher LM
通讯作者：
Hutt-Fletcher LM
影响因子：
6.8
作者：
Backovic, Marija;Jardetzky, Theodore S.
通讯作者：
Jardetzky, Theodore S.
影响因子：
16.8
作者：
Dong, Xianchi;Hudson, Nathan E.;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
6.4
作者：
Chen, Jia;Rowe, Cynthia L.;Longnecker, Richard
通讯作者：
Longnecker, Richard