9LU3

LN1F9 Fab bound to Nipah Virus attachment (G) glycoprotein head domain

Summary for 9LU3

• Entry DOI: 10.2210/pdb9lu3/pdb
• Descriptor: Glycoprotein G, mAb LN1F9 Fab heavy chain, mAb LN1F9 Fab light chain, ... (4 entities in total)
• Functional Keywords: glycoprotein g, fab, viral protein/immune system, viral protein-immune system complex
• Biological source: Henipavirus nipahense; More
• Total number of polymer chains: 6
• Total formula weight: 198639.01

Authors

Deng, Z.,Kuang, W. (deposition date: 2025-02-07, 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

X-RAY DIFFRACTION (3 Å)