8JR5

Crystal structure of Hendra Virus attachment(G) glycoprotein mutant S586N

Summary for 8JR5

• Entry DOI: 10.2210/pdb8jr5/pdb
• Descriptor: Glycoprotein G, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: hendra virus, nipah virus, attachment glycoprotein, viral protein
• Biological source: Hendra virus (isolate Horse/Autralia/Hendra/1994)
• Total number of polymer chains: 2
• Total formula weight: 94923.51

Authors

Li, Y.H.,Huang, X.Y.,Xu, J.J.,Chen, W. (deposition date: 2023-06-16, release date: 2024-06-19, Last modification date: 2025-12-31)

Primary citation

Li, Y.,Huang, X.,Li, R.,Zai, X.,Yang, Y.,Zhang, Y.,Zhang, Z.,Zhang, J.,Xu, J.,Chen, W.
Single amino acid substitution in Hendra virus attachment glycoprotein induces cross-neutralizing antibodies against Nipah virus.
Signal Transduct Target Ther, 10:276-276, 2025

PubMed Abstract: Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses within the Paramyxoviridae family, causing severe respiratory and neurological diseases in humans and animals with fatality rates up to 75%, and no licensed human vaccines or therapeutics. In this study, we identified a unique vulnerable epitope on the NiV attachment glycoprotein (G) recognized by the potent neutralizing antibody 14F8, which targets a receptor-binding site and neutralizes NiV effectively. Using the 2.8 Å crystal structure of the 14F8 Fab-NiV-G complex as a guide, we reconstructed this epitope on HeV-G via a single amino acid substitution (S586N), creating the HeV-G mutant. Immunization with HeV-G in BALB/c mice and cynomolgus monkeys elicited robust, broadly neutralizing antibody responses against both NiV and HeV, achieving higher NiV-neutralizing titers post-prime compared to wild-type HeV-G, as confirmed by pseudovirus and live-virus assays. Crystal structures of HeV-G (3.3 Å) and its 14F8 complex (3.2 Å) showed the S586N substitution induced a 9 Å conformational rearrangement in β-propeller blade 6, reshaping the molecular skeleton and solvent-accessible surface without direct N586-14F8 interaction, thus mimicking the NiV epitope. These findings position HeV-G as a promising broad-spectrum antigen for henipavirus prevention and demonstrate the value of structure-guided epitope reconstruction in universal vaccine design for emerging viral threats.

PubMed: 40877258
DOI: 10.1038/s41392-025-02370-0

Experimental method

X-RAY DIFFRACTION (3.3 Å)