Transient opening of trimeric prefusion RSV F proteins
Transient opening of trimeric prefusion RSV F proteins
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DOI：
10.1038/s41467-019-09807-5
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发表时间：
2019-05-08
影响因子：
16.6
通讯作者：
McLellan, Jason S.
中科院分区：
文献类型：
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作者：
Gilman, Morgan S. A.;Furmanova-Hollenstein, Polina;McLellan, Jason S.
呼吸道合胞病毒（RSV）F糖蛋白是介导病毒进入的I类融合蛋白，并且是中和抗体的主要靶标。RSV F的融合前形式以及其他I类融合蛋白的结构已经揭示了紧凑的三聚体排列，然而这些三聚体形式是否可以瞬时打开仍然是未知的。在这里，我们对最近分离的抗体CR9501进行了结构和生化研究，并证明它增强了融合前稳定的RSV F三聚体的开放。结合CR9501的单体RSV F的3.3埃晶体结构，结合超过25个先前确定的RSV F结构的分析，揭示了融合前构象的呼吸运动。我们还证明了全长RSV F三聚体在细胞表面瞬时打开并解离。总的来说，这些发现对I类融合蛋白的功能以及RSV的抗体预防和疫苗开发具有意义。
The respiratory syncytial virus (RSV) F glycoprotein is a class I fusion protein that mediates viral entry and is a major target of neutralizing antibodies. Structures of prefusion forms of RSV F, as well as other class I fusion proteins, have revealed compact trimeric arrangements, yet whether these trimeric forms can transiently open remains unknown. Here, we perform structural and biochemical studies on a recently isolated antibody, CR9501, and demonstrate that it enhances the opening of prefusion-stabilized RSV F trimers. The 3.3 angstrom crystal structure of monomeric RSV F bound to CR9501, combined with analysis of over 25 previously determined RSV F structures, reveals a breathing motion of the prefusion conformation. We also demonstrate that full-length RSV F trimers transiently open and dissociate on the cell surface. Collectively, these findings have implications for the function of class I fusion proteins, as well as antibody prophylaxis and vaccine development for RSV.