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TitleFlavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 1238, Year 2021
Publish dateFeb 23, 2021
AuthorsMax Renner / Wanwisa Dejnirattisai / Loïc Carrique / Itziar Serna Martin / Dimple Karia / Serban L Ilca / Shu F Ho / Abhay Kotecha / Jeremy R Keown / Juthathip Mongkolsapaya / Gavin R Screaton / Jonathan M Grimes /
PubMed AbstractFlaviviruses 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 ...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.
External linksNat Commun / PubMed:33623019 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 7.8 Å
Structure data

11364

6zqi

EMDB-11364, PDB-6zqi:
Cryo-EM structure of Spondweni virus prME
Method: EM (single particle) / Resolution: 3.8 Å

11366

6zqj

EMDB-11366, PDB-6zqj:
Cryo-EM structure of trimeric prME spike of Spondweni virus
Method: EM (single particle) / Resolution: 4.2 Å

11370

6zqu

EMDB-11370, PDB-6zqu:
Cryo-EM structure of mature Dengue virus 2 at 3.1 angstrom resolution
Method: EM (single particle) / Resolution: 3.1 Å

11371

6zqv

EMDB-11371, PDB-6zqv:
Cryo-EM structure of mature Spondweni virus
Method: EM (single particle) / Resolution: 2.6 Å

11372

6zqw

EMDB-11372, PDB-6zqw:
Cryo-EM structure of immature Spondweni virus
Method: EM (single particle) / Resolution: 7.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

Source
  • spondweni virus
  • dengue virus 2
KeywordsVIRUS / Flavivirus

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