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TitleVisualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 4772, Year 2022
Publish dateAug 15, 2022
AuthorsVidya Mangala Prasad / Jelle S Blijleven / Jolanda M Smit / Kelly K Lee /
PubMed AbstractChikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though ...Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, structural characterization of virion interaction with membranes has been limited. Here, we have used cryo-electron tomography to visualize CHIKV's complete membrane fusion pathway, identifying key intermediary glycoprotein conformations coupled to membrane remodeling events. Using sub-tomogram averaging, we elucidate features of the low pH-exposed virion, nucleocapsid and full-length E1-glycoprotein's post-fusion structure. Contrary to class-I fusion systems, CHIKV achieves membrane apposition by protrusion of extended E1-glycoprotein homotrimers into the target membrane. The fusion process also features a large hemifusion diaphragm that transitions to a wide pore for intact nucleocapsid delivery. Our analyses provide comprehensive ultrastructural insights into the class-II virus fusion system function and direct mechanistic characterization of the fundamental process of protein-mediated membrane fusion.
External linksNat Commun / PubMed:35970990 / PubMed Central
MethodsEM (subtomogram averaging) / EM (single particle)
Resolution6.75 - 27.2 Å
Structure data

27248

8d87

EMDB-27248: Sub-tomogram averaged map of full-length post-fusion CHIKV E1 glycoprotein trimer
PDB-8d87: Fitted crystal structure of the homotrimer of fusion glycoprotein E1 from SFV into subtomogram averaged CHIKV E1 glycoprotein density
Method: EM (subtomogram averaging) / Resolution: 27.2 Å

EMDB-27559: Cryo-EM map of Chikungunya virus strain s27
Method: EM (single particle) / Resolution: 6.75 Å

Chemicals

ChemComp-BR:
BROMIDE ION

ChemComp-HO:
HOLMIUM ATOM

ChemComp-PO4:
PHOSPHATE ION

ChemComp-HOH:
WATER

Source
  • chikungunya virus strain s27-african prototype
KeywordsVIRAL PROTEIN / envelope glycoprotein / membrane fusion / virus

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