Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus
Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus
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DOI：
10.1371/journal.pone.0032186
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发表时间：
2012-02-23
期刊：
影响因子：
3.7
通讯作者：
Galdiero, Stefania
中科院分区：
文献类型：
--
作者：
Falanga, Annarita;Tarallo, Rossella;Galdiero, Stefania
疱疹病毒侵入的分子机制需要一个多组分的融合系统。单纯疱疹病毒(HSV)的细胞侵袭需要四种病毒编码的糖蛋白：gD、gB和Gh/g1。GB的作用一直难以捉摸，直到最近HSV-1 gB的晶体结构变得可用，gB的融合潜力才被清楚地展示出来。尽管近年来已经收集了大量关于gB结构/功能关系的信息，但阐明gB融合环与膜双层之间精细相互作用的本质可能有助于理解疱疹病毒与宿主细胞膜融合的确切分子机制。在这里，我们首次报道了GB的两个融合肽的生物物理研究，特别是这两个肽对不同组成的脂双层的影响。两个融合环构成一个结构亚域，其中关键的疏水氨基酸形成一个脊状结构，两侧由带电残基支撑。当两个融合环一起使用时，尽管单独使用时它们的双层渗透率较低，但仍有能力显著破坏靶膜双层的稳定性。这些数据支持GB融合环插入胆固醇富集膜的模型。
The molecular mechanism of entry of herpesviruses requires a multicomponent fusion system. Cell invasion by Herpes simplex virus (HSV) requires four virally encoded glycoproteins: namely gD, gB and gH/gL. The role of gB has remained elusive until recently when the crystal structure of HSV-1 gB became available and the fusion potential of gB was clearly demonstrated. Although much information on gB structure/function relationship has been gathered in recent years, the elucidation of the nature of the fine interactions between gB fusion loops and the membrane bilayer may help to understand the precise molecular mechanism behind herpesvirus-host cell membrane fusion. Here, we report the first biophysical study on the two fusion peptides of gB, with a particular focus on the effects determined by both peptides on lipid bilayers of various compositions. The two fusion loops constitute a structural subdomain wherein key hydrophobic amino acids form a ridge that is supported on both sides by charged residues. When used together the two fusion loops have the ability to significantly destabilize the target membrane bilayer, notwithstanding their low bilayer penetration when used separately. These data support the model of gB fusion loops insertion into cholesterol enriched membranes.