9LUE

Cryo-EM structure of the Nipah G head domain in complex with three Fabs

Summary for 9LUE

• Entry DOI: 10.2210/pdb9lue/pdb
• EMDB information: 63395
• Descriptor: Glycoprotein G, NIV LN3D3 Fab Light Chain, NiV S2B10 Fab Heavy Chain, ... (8 entities in total)
• Functional Keywords: nipah g protein, antibodies, viral protein/immune system, viral protein-immune system complex
• Biological source: Henipavirus nipahense; More
• Total number of polymer chains: 7
• Total formula weight: 124869.53

Authors

Wang, Y.,Deng, Z.,Zhao, H. (deposition date: 2025-02-08, release date: 2025-11-26, Last modification date: 2026-01-21)

Primary citation

Zhou, D.,Wang, Y.,Yao, Y.,Kuang, W.,Cheng, R.,Zhang, G.,Liu, H.,Li, X.,Chiu, S.,Deng, Z.,Zhao, H.
Antigenic landscape of Nipah virus attachment glycoprotein analysis reveals a protective immunodominant epitope across species.
Npj Vaccines, 11:5-5, 2025

PubMed Abstract: Nipah virus (NiV) and Hendra virus (HeV), two highly pathogenic Henipaviruses (HNVs), pose a significant public health threat. The attachment glycoprotein (G) plays a crucial role in viral attachment and entry, making it an attractive target for vaccine and therapeutic antibody development. However, the antigenic landscape and neutralization sensitivity of the diverse HNV G proteins remain poorly defined. Here, we systematically characterize 27 monoclonal antibodies (mAbs) elicited by NiV G head (G) nanoparticle-immunized mice. Among these, 25 mAbs exhibit neutralizing activity against two major NiV strains, NiV-Malaysia and NiV-Bangladesh, with five mAbs also cross-inhibiting HeV infection. Notably, mAbs from two distinct groups conferred complete protection to hamsters against lethal NiV-Malaysia challenge. Structural analysis of NiV G in complex with representative Fabs reveals four non-overlapping epitopes, including two novel antigenic sites and one public protective epitope shared across species. MAbs targeting the novel sites bind to the top or side faces of G protein's β-propeller and inhibit viral infection by blocking either receptor engagement or membrane fusion. MAbs recognizing the public epitope block the receptor binding directly. Our study provides a comprehensive antigenic map of the NiV G and offers new insights and opportunities for antibody-based therapies and rational vaccine development.

PubMed: 41315143
DOI: 10.1038/s41541-025-01319-2

Experimental method

ELECTRON MICROSCOPY (3.03 Å)