Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus.
Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus.
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辛德比斯病毒中 E2 包膜糖蛋白和核衣壳核心之间的分子联系。
DOI：
10.1016/j.jmb.2011.09.045
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发表时间：
2011
影响因子：
5.6
通讯作者：
Baker,TimothyS
中科院分区：
文献类型：
--
作者：
Tang,Jinghua;Jose,Joyce;Chipman,Paul;Zhang,Wei;Kuhn,RichardJ;Baker,TimothyS
本文介绍的Sindbis病毒7.0 Å分辨率的三维重建提供了病毒粒子结构的详细视图，并包括衣壳蛋白（CP）和跨膜糖蛋白（TM） E1和E2之间发生的关键相互作用的结构证据。基于组成蛋白的晶体结构和同源性建模，我们构建了一个近乎完整的病毒伪原子模型。值得注意的是，这包括鉴定E2的33个残基细胞质结构域（cdE2），它遵循从E2 TM螺旋到CP的路径，在那里它进入和退出CP疏水袋，然后折叠回来与病毒膜接触。模型分析确定了cdE2和CP之间的三个主要接触区域，并通过分子遗传学探讨了特定残基的作用。这证实了cdE2的R393和E395以及CP的Y162和K252是病毒组装的关键。CP的n端形成一个连续的网络，连接12个五聚体和30个六聚体。一个糖蛋白刺突与三个相邻的CP衣壳体交联，这可能发生在病毒出芽开始时。
A three-dimensional reconstruction of Sindbis virus at 7.0 Å resolution presented here provides a detailed view of the virion structure and includes structural evidence for key interactions that occur between the capsid protein (CP) and transmembrane (TM) glycoproteins E1 and E2. Based on crystal structures of component proteins and homology modeling, we constructed a nearly complete, pseudo-atomic model of the virus. Notably, this includes identification of the 33-residue cytoplasmic domain of E2 (cdE2), which follows a path from the E2 TM helix to the CP where it enters and exits the CP hydrophobic pocket and then folds back to contact the viral membrane. Modeling analysis identified three major contact regions between cdE2 and CP, and the roles of specific residues were probed by molecular genetics. This identified R393 and E395 of cdE2 and Y162 and K252 of CP as critical for virus assembly. The N-termini of the CPs form a contiguous network that interconnects 12 pentameric and 30 hexameric CP capsomers. A single glycoprotein spike cross-links three neighboring CP capsomers as might occur during initiation of virus budding.