6T3F

Crystal structure Nipah virus fusion glycoprotein in complex with a neutralising Fab fragment

6T3F の概要

• エントリーDOI: 10.2210/pdb6t3f/pdb
• 分子名称: Fusion glycoprotein F0, Fab66 light chain, Fab66 heavy chain, ... (5 entities in total)
• 機能のキーワード: fusion protein, glycoprotein, antibody, fab, viral protein
• 由来する生物種: Nipah virus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 103688.02

構造登録者

Avanzato, V.A.,Pryce, R.,Walter, T.S.,Bowden, T.A. (登録日: 2019-10-10, 公開日: 2019-11-27, 最終更新日: 2024-11-20)

主引用文献

Avanzato, V.A.,Oguntuyo, K.Y.,Escalera-Zamudio, M.,Gutierrez, B.,Golden, M.,Kosakovsky Pond, S.L.,Pryce, R.,Walter, T.S.,Seow, J.,Doores, K.J.,Pybus, O.G.,Munster, V.J.,Lee, B.,Bowden, T.A.
A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.
Proc.Natl.Acad.Sci.USA, 116:25057-25067, 2019

PubMed Abstract: Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F-specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F-nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.

PubMed: 31767754
DOI: 10.1073/pnas.1912503116

実験手法

X-RAY DIFFRACTION (3.2 Å)