A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.

Abstract

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.

DOI: 10.1126/science.aal2712

Cite this paper

@article{GuardadoCalvo2017AGP, title={A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion.}, author={Pablo Guardado-Calvo and Kalina Atkovska and S A Jeffers and Nicole Grau and M Backovic and J P{\'e}rez-Vargas and S M de Boer and M A Tortorici and G{\'e}rard P{\'e}hau-Arnaudet and Jean Lepault and Patrick England and Peter J. M. Rottier and B J Bosch and Jochen S. Hub and Felix Rey}, journal={Science}, year={2017}, volume={358 6363}, pages={663-667} }