7KI4

Structure of the NiV F glycoprotein in complex with the 12B2 neutralizing antibody

Summary for 7KI4

• Entry DOI: 10.2210/pdb7ki4/pdb
• EMDB information: 22884
• Descriptor: Fusion glycoprotein F0, 12B2 Fab light chain, 12B2 heavy chain, ... (6 entities in total)
• Functional Keywords: nipah virus, hendra virus, henipavirus, neutralizing antibody, monoclonal antibody, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Nipah virus; More
• Total number of polymer chains: 9
• Total formula weight: 404424.57

Authors

Dang, H.V.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2020-10-23, release date: 2021-05-05, Last modification date: 2024-11-13)

Primary citation

Dang, H.V.,Cross, R.W.,Borisevich, V.,Bornholdt, Z.A.,West, B.R.,Chan, Y.P.,Mire, C.E.,Da Silva, S.C.,Dimitrov, A.S.,Yan, L.,Amaya, M.,Navaratnarajah, C.K.,Zeitlin, L.,Geisbert, T.W.,Broder, C.C.,Veesler, D.
Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins.
Nat.Struct.Mol.Biol., 28:426-434, 2021

PubMed Abstract: 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.

PubMed: 33927387
DOI: 10.1038/s41594-021-00584-8

Experimental method

ELECTRON MICROSCOPY (2.9 Å)