Halldorsson Steinar, Li Sai, Li Mengqiu, Harlos Karl, Bowden Thomas A, Huiskonen Juha T
Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Helsinki Institute of Life Science and Faculty of Environmental and Biological Sciences, University of Helsinki, Viikinkaari 1, Helsinki, 00014, Finland.
Nat Commun. 2018 Jan 24;9(1):349. doi: 10.1038/s41467-017-02789-2.
Entry of enveloped viruses relies on insertion of hydrophobic residues of the viral fusion protein into the host cell membrane. However, the intermediate conformations during fusion remain unknown. Here, we address the fusion mechanism of Rift Valley fever virus. We determine the crystal structure of the Gn glycoprotein and fit it with the Gc fusion protein into cryo-electron microscopy reconstructions of the virion. Our analysis reveals how the Gn shields the hydrophobic fusion loops of the Gc, preventing premature fusion. Electron cryotomography of virions interacting with membranes under acidic conditions reveals how the fusogenic Gc is activated upon removal of the Gn shield. Repositioning of the Gn allows extension of Gc and insertion of fusion loops in the outer leaflet of the target membrane. These data show early structural transitions that enveloped viruses undergo during host cell entry and indicate that analogous shielding mechanisms are utilized across diverse virus families.
包膜病毒的进入依赖于病毒融合蛋白的疏水残基插入宿主细胞膜。然而，融合过程中的中间构象仍然未知。在这里，我们研究裂谷热病毒的融合机制。我们确定了Gn糖蛋白的晶体结构，并将其与Gc融合蛋白一起拟合到病毒粒子的冷冻电子显微镜重建中。我们的分析揭示了Gn如何屏蔽Gc的疏水融合环，防止过早融合。在酸性条件下与膜相互作用的病毒粒子的电子冷冻断层扫描揭示了在去除Gn屏蔽后促融合的Gc是如何被激活的。Gn的重新定位允许Gc伸展并将融合环插入靶膜的外小叶。这些数据显示了包膜病毒在宿主细胞进入过程中经历的早期结构转变，并表明不同病毒家族利用了类似的屏蔽机制。
