7KI4

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

7KI4 の概要

• エントリーDOI: 10.2210/pdb7ki4/pdb
• EMDBエントリー: 22884
• 分子名称: Fusion glycoprotein F0, 12B2 Fab light chain, 12B2 heavy chain, ... (6 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Nipah virus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 404424.57

構造登録者

Dang, H.V.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2020-10-23, 公開日: 2021-05-05, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.9 Å)