A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion
A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion
复制标题
DOI：
10.1126/science.aal2712
复制
发表时间：
2017-11-03
期刊：
影响因子：
56.9
通讯作者：
Rey, F. A.
中科院分区：
文献类型：
--
作者：
Guardado-Calvo, P.;Atkovska, K.;Rey, F. A.
裂谷热病毒(RVFV)由受感染的蚊子传播，在非洲各地的人和牲畜中造成严重疾病。我们测定了RVFV II类融合蛋白GC在融合后的X射线结构，以及在融合环旁边的保守空腔中与甘油磷脂(GPL)结合的复合体。定点突变和分子动力学模拟进一步揭示了一个内置的基序，允许融合环整体插入膜中，在膜重组时，与脂族部分的非极性侧链相互作用很少，与脂头基团的多极性相互作用。GPL头群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，这两种病毒最近在全球范围内造成了重大流行病。
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.