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Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins
- 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.
- Subjects :
- Models, Molecular
0301 basic medicine
Science
viruses
medicine.medical_treatment
General Physics and Astronomy
Dengue virus
medicine.disease_cause
Protein Structure, Secondary
Article
General Biochemistry, Genetics and Molecular Biology
Dengue fever
Zika virus
03 medical and health sciences
0302 clinical medicine
Electron microscopy
medicine
Amino Acid Sequence
Furin
Histidine
Spondweni virus
Membrane Glycoproteins
Multidisciplinary
Protease
biology
Flavivirus
virus diseases
General Chemistry
biochemical phenomena, metabolism, and nutrition
medicine.disease
biology.organism_classification
Lipids
3. Good health
Cell biology
030104 developmental biology
biology.protein
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....cf25a7d74adecd680155faeb418032fa