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TitleEngineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes.
Journal, issue, pagesCell, Vol. 188, Issue 2, Page 303-315.e13, Year 2025
Publish dateJan 23, 2025
AuthorsElizabeth McFadden / Stephanie R Monticelli / Albert Wang / Ajit R Ramamohan / Thomas G Batchelor / Ana I Kuehne / Russell R Bakken / Alexandra L Tse / Kartik Chandran / Andrew S Herbert / Jason S McLellan /
PubMed AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne virus that can cause severe disease in humans with case fatality rates of 10%-40%. Although structures of CCHFV glycoproteins GP38 and Gc ...Crimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne virus that can cause severe disease in humans with case fatality rates of 10%-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we use structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-Gn-Gc). A cryo-electron microscopy (cryo-EM) structure of this complex provides the molecular basis for GP38's association on the viral surface, reveals the structure of Gn, and demonstrates that GP38-Gn restrains the Gc fusion loops in the prefusion conformation, facilitated by an N-linked glycan attached to Gn. Immunization with GP38-Gn-Gc conferred 40% protection against lethal IbAr10200 challenge in mice. These data define the architecture of a GP38-Gn-Gc protomer and provide a template for structure-guided vaccine antigen development.
External linksCell / PubMed:39701101 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.5 - 3.4 Å
Structure data

44347

9b8j

EMDB-44347, PDB-9b8j:
GP38-GnH-DS-Gc in the pre-fusion conformation
Method: EM (single particle) / Resolution: 3.4 Å

PDB-9avf:
CCHFV GP38-GnH-DS heterodimer
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

Chemicals

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

ChemComp-A2G:
2-acetamido-2-deoxy-alpha-D-galactopyranose

ChemComp-HOH:
WATER

Source
  • Orthonairovirus haemorrhagiae
  • crimean-congo hemorrhagic fever virus strain ibar10200
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Crimean-Congo Hemorrhagic Fever Virus / CCHFV / GP38 / Gn / glycoprotein / GP38-Gn / ancestral heterodimer / GPC / fusion loops / accompanying protein / Gc / pre-fusion / heterotrimer / GP38-Gn-Gc / Gn-Gc / GP38/Gn/Gc / Gn/Gc / GP38/Gn

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