8XC4

Nipah virus attachment glycoprotein head domain in complex with a broadly neutralizing antibody 1E5

Summary for 8XC4

• Entry DOI: 10.2210/pdb8xc4/pdb
• Descriptor: Glycoprotein, 1E5-VH, 1E5-VL, ... (8 entities in total)
• Functional Keywords: henipavirus, glycoprotein, head domain, antibody, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Henipavirus nipahense; More
• Total number of polymer chains: 6
• Total formula weight: 202349.74

Authors

Fan, P.F.,Yu, C.M.,Chen, W. (deposition date: 2023-12-08, release date: 2024-01-24, Last modification date: 2024-10-30)

Primary citation

Fan, P.,Sun, M.,Zhang, X.,Zhang, H.,Liu, Y.,Yao, Y.,Li, M.,Fang, T.,Sun, B.,Chen, Z.,Chi, X.,Chen, L.,Peng, C.,Chen, Z.,Zhang, G.,Ren, Y.,Liu, Z.,Li, Y.,Li, J.,Li, E.,Guan, W.,Li, S.,Gong, R.,Zhang, K.,Yu, C.,Chiu, S.
A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.
Nat Commun, 15:4330-4330, 2024

PubMed Abstract: The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop β1S2-β1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.

PubMed: 38773072
DOI: 10.1038/s41467-024-48601-w

Experimental method

X-RAY DIFFRACTION (3.24 Å)