Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
Virology. 2014 Apr;454-455:93-101. doi: 10.1016/j.virol.2014.02.015. Epub 2014 Feb 25.
The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1-E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain.
病毒包膜蛋白的膜锚在细胞进入中起着至关重要的作用。最近来自一种瘟病毒的包膜蛋白 E2 的外域的晶体结构表明，E2 属于一种新型的膜融合机制的结构类别。基于 E2 结构的几何约束，我们使用计算方法生成了 E1 和 E2 膜锚的原子模型。E1 锚含有两个两亲性的跨膜螺旋和一个跨膜螺旋；E2 锚含有一个短的螺旋发夹，由精氨酸残基稳定在膜中，类似于黄病毒。E2 外域中的一对组氨酸残基可能参与 pH 感应。提出的原子模型表明 E2 中的 Cys987 是与 E1 形成 E1-E2 异二聚体的二硫键连接位点。膜锚模型为 E1 外域的二硫键连接模式和整体骨架构象提供了结构约束。
