Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 02 2021
23 02 2021
Historique:
received:
28
10
2020
accepted:
28
01
2021
entrez:
24
2
2021
pubmed:
25
2
2021
medline:
4
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33623019
doi: 10.1038/s41467-021-21505-9
pii: 10.1038/s41467-021-21505-9
pmc: PMC7902656
doi:
Substances chimiques
Lipids
0
Membrane Glycoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1238Subventions
Organisme : Wellcome Trust
ID : 200835/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 093305/Z/10/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 075491/Z/04
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 060208/Z/00/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204703/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : 1374922
Pays : United Kingdom
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