7ki6

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Structure of the HeV F glycoprotein in complex with the 1F5 neutralizing antibody

Structural highlights

7ki6 is a 9 chain structure with sequence from Henipavirus hendraense and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.8Å
Ligands:NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.

Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins.,Dang HV, Cross RW, Borisevich V, Bornholdt ZA, West BR, Chan YP, Mire CE, Da Silva SC, Dimitrov AS, Yan L, Amaya M, Navaratnarajah CK, Zeitlin L, Geisbert TW, Broder CC, Veesler D Nat Struct Mol Biol. 2021 May;28(5):426-434. doi: 10.1038/s41594-021-00584-8. , Epub 2021 Apr 29. PMID:33927387[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. Dang HV, Cross RW, Borisevich V, Bornholdt ZA, West BR, Chan YP, Mire CE, Da Silva SC, Dimitrov AS, Yan L, Amaya M, Navaratnarajah CK, Zeitlin L, Geisbert TW, Broder CC, Veesler D. Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins. Nat Struct Mol Biol. 2021 May;28(5):426-434. PMID:33927387 doi:10.1038/s41594-021-00584-8

Contents


PDB ID 7ki6

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