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Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins

Authors :
Loic Carrique
Jonathan M. Grimes
Abhay Kotecha
Gavin R. Screaton
D. Karia
Serban L. Ilca
S.F. Ho
Juthathip Mongkolsapaya
J.R. Keown
Itziar Serna Martin
Wanwisa Dejnirattisai
Max Renner
Source :
Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-9 (2021)
Publication Year :
2021
Publisher :
Springer Science and Business Media LLC, 2021.

Abstract

Flaviviruses such as Dengue (DENV) or Zika virus (ZIKV) assemble into an immature form within the endoplasmatic reticulum (ER), and are then processed by furin protease in the trans-Golgi. To better grasp maturation, we carry out cryo-EM reconstructions of immature Spondweni virus (SPOV), a human flavivirus of the same serogroup as ZIKV. By employing asymmetric localised reconstruction we push the resolution to 3.8 Å, enabling us to refine an atomic model which includes the crucial furin protease recognition site and a conserved Histidine pH-sensor. For direct comparison, we also solve structures of the mature forms of SPONV and DENV to 2.6 Å and 3.1 Å, respectively. We identify an ordered lipid that is present in only the mature forms of ZIKV, SPOV, and DENV and can bind as a consequence of rearranging amphipathic stem-helices of E during maturation. We propose a structural role for the pocket and suggest it stabilizes mature E.<br />Here, the authors provide cryo-EM structures of mature and immature Spondweni virus, defining the furin recognition site at high resolution, and identifying a lipid that binds E upon capsid maturation and is also present in Zika and Dengue virions.

Details

ISSN :
20411723
Volume :
12
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....cf25a7d74adecd680155faeb418032fa