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.
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Article dans une revue
Science, American Association for the Advancement of Science, 2017, 358 (6363), pp.663 - 667. 〈10.1126/science.aal2712〉
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Contributeur : Marija Backovic <>
Soumis le : vendredi 10 novembre 2017 - 17:01:39
Dernière modification le : jeudi 15 mars 2018 - 15:06:52

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P. Guardado-Calvo, K. Atkovska, S. A. Jeffers, N. Grau, M. Backovic, et al.. A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion. Science, American Association for the Advancement of Science, 2017, 358 (6363), pp.663 - 667. 〈10.1126/science.aal2712〉. 〈pasteur-01632899〉

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