Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, 75724 Paris Cedex 15, France.
UMR 3569 Virologie, CNRS-Institut Pasteur, 25-28 Rue du Docteur Roux, 75015 Paris, France.
Science. 2017 Nov 3;358(6363):663-667. doi: 10.1126/science.aal2712.
The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide.
裂谷热病毒（RVFV）通过受感染的蚊子传播，在非洲导致人类和牲畜的严重疾病。我们确定了 RVFV 类 II 融合蛋白 Gc 的 X 射线结构，其处于融合后形式，并与结合在融合环旁边保守腔中的甘油磷脂（GPL）复合。定点突变和分子动力学模拟进一步揭示了一个内置的模体，允许融合环整体插入膜中，与脂肪部分只有很少的非极性侧链相互作用，并在膜重排时与脂质头基形成多个极性相互作用。GPL 头基识别口袋在其他节肢动物传播病毒的融合蛋白中保守，如寨卡病毒和基孔肯雅病毒，这些病毒最近在全球范围内引起了重大疫情。
