HIV-1 传播的创始包膜三聚体结构中的隔离融合肽。
A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer.
机构信息
Department of Biology, The Catholic University of America, Washington, DC, 20064, USA.
Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
出版信息
Nat Commun. 2019 Feb 20;10(1):873. doi: 10.1038/s41467-019-08825-7.
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-Å 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.
人类免疫缺陷病毒 1（HIV-1）的包膜蛋白及其融合肽对于细胞进入和疫苗设计至关重要。在这里，我们描述了一种非常早期传播的创始病毒（CRF01_AE T/F100）与广谱中和抗体（bNAb）8ANC195 的 Fab 复合物的包膜蛋白三聚体的 3.9Å 分辨率结构。总体而言，T/F100 三聚体结构与其他报道的“封闭”状态前融合三聚体结构相似。相比之下，融合肽在报道的封闭结构中暴露于溶剂中，被封闭在 T/F100 三聚体的疏水核心中。以前在 CD4 受体结合后形成的“开放”状态结构中观察到了埋藏构象。T/F100 三聚体与包括融合肽特异性 bNAb PGT151 和 VRC34.01 在内的 bNAb 结合不良。T/F100 结构可能代表了一种前融合状态，处于封闭和开放状态之间。这些观察结果与 HIV-1 传播和疫苗设计的机制有关。
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