Lassa virus glycoprotein: stopping a moving target
Lassa virus glycoprotein: stopping a moving target
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DOI：
10.1016/j.coviro.2018.05.002
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发表时间：
2018-08-01
影响因子：
5.9
通讯作者：
Saphire, Erica Mann
中科院分区：
文献类型：
--
作者：
Hastie, Kathryn M.;Saphire, Erica Mann
由于受体结合亚基和融合亚基之间的亚稳和非共价性质，融合病毒GPC的结构多年来一直是个谜。最近的工程工作稳定了旧大陆阿拉伯病毒LassA的糖蛋白，使其处于天然但被切割的状态，从而确定了任何病毒预融合GPC三聚体的第一结构。将这种结构与其他ArenaVirus糖蛋白亚基的结构进行比较，发现了令人惊讶的发现：拉萨病毒的受体结合亚基GP1是构象不稳定的，而新大陆ArenaVirus的GP1亚基不是，而且ArenaVirus GPC与其他具有类似融合机制的糖蛋白不同，采用三聚体状态。结构分析，结合最近关于抗体表位和受体结合要求的生化数据，为合理的疫苗设计提供了基础。
The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.