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© Research
Publication : Science (New York, N.Y.)

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Science (New York, N.Y.) - 03 Nov 2017

Guardado-Calvo P, Atkovska K, Jeffers SA, Grau N, Backovic M, Pérez-Vargas J, de Boer SM, Tortorici MA, Pehau-Arnaudet G, Lepault J, England P, Rottier PJ, Bosch BJ, Hub JS, Rey FA,

Link to Pubmed [PMID] – 29097548

Link to DOI – 10.1126/science.aal2712

Science 2017 Nov; 358(6363): 663-667

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.