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TitleStructure and design of Langya virus glycoprotein antigens.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 16, Page e2314990121, Year 2024
Publish dateApr 16, 2024
AuthorsZhaoqian Wang / Matthew McCallum / Lianying Yan / Cecily A Gibson / William Sharkey / Young-Jun Park / Ha V Dang / Moushimi Amaya / Ashley Person / Christopher C Broder / David Veesler /
PubMed AbstractLangya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which ...Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.
External linksProc Natl Acad Sci U S A / PubMed:38593070 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.9 Å
Structure data

EMDB-41636, PDB-8tvb:
Ghanaian virus fusion glycoprotein (GhV F)
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-41639, PDB-8tve:
Langya henipavirus fusion protein in postfusion state
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-41640, PDB-8tvf:
Langya henipavirus fusion protein in prefusion state
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-41641, PDB-8tvg:
Langya henipavirus postfusion F protein in complex with the 4G5 Fab, local refinement of the viral membrane distal region
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-41642, PDB-8tvh:
Langya henipavirus postfusion F protein in complex with 4G5 Fab, local refinement of the viral membrane proximal region
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-41643, PDB-8tvi:
Langya Virus G glycoprotein (LayV G) with stabilizing mutations
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-41644: Langya henipavirus postfusion fusion protein in complex with 4G5 Fab (global refinement)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-43593, PDB-8vwp:
Langya Virus attachment (G) glycoprotein with K85L/L86K mutation
Method: EM (single particle) / Resolution: 3.21 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

ChemComp-ZN:
Unknown entry

Source
  • henipavirus ghanaense
  • thermotoga maritima msb8 (bacteria)
  • langya virus
  • mus musculus (house mouse)
  • Mus sp. (mice)
KeywordsVIRAL PROTEIN / GhV F / Glycoprotein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Inhibitor / VIRAL PROTEIN-IMMUNE SYSTEM complex / Langya / henipavirus / fusion protein / postfusion / LayVF / prefusion / VIRAL PROTEIN/IMMUNE SYSTEM / LayVG / LayV / G protein / attachment protein / attachment glycoprotein / Langya virus / protein design / protein stabilization / attachment

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