A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer
A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer
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DOI：
10.1038/s41467-019-08825-7
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发表时间：
2019-02-20
影响因子：
16.6
通讯作者：
Rao, Venigalla B.
中科院分区：
文献类型：
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作者：
Ananthaswamy, Neeti;Fang, Qianglin;Rao, Venigalla B.
人类免疫缺陷病毒1型（HIV-1）的包膜蛋白及其融合肽对于细胞进入和疫苗设计是必不可少的。在这里，我们描述了3.9埃分辨率结构的包膜蛋白三聚体从非常早期传播的创始人病毒（CRF01_AE T/F100）与Fab从广泛中和抗体（bNAb）8ANC 195复合。整体T/F100三聚体结构类似于其它报道的“闭合”状态的融合前三聚体结构。相反，在报道的封闭结构中暴露于溶剂的融合肽被隔离（掩埋）在T/F100三聚体的疏水核心中。以前在CD 4受体结合后形成的“开放”状态结构中观察到了掩埋构象。T/F100三聚体与包括融合肽特异性bNAb PGT 151和VRC34.01的bNAb结合较差。T/F100结构可能代表融合前状态，介于闭合和开放状态之间。这些观察结果与HIV-1传播机制和疫苗设计有关。
The envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-angstrom resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195. The overall T/F100 trimer structure is similar to other reported "closed" state prefusion trimer structures. In contrast, the fusion peptide, which is exposed to solvent in reported closed structures, is sequestered (buried) in the hydrophobic core of the T/F100 trimer. A buried conformation has previously been observed in "open" state structures formed after CD4 receptor binding. The T/F100 trimer binds poorly to bNAbs including the fusion peptide-specific bNAbs PGT151 and VRC34.01. The T/F100 structure might represent a prefusion state, intermediate between the closed and open states. These observations are relevant to mechanisms of HIV-1 transmission and vaccine design.