8k0d | pdb_00008k0d
Cryo-EM structure of conformation 2 of complex of Nipah virus attachment G with 1E5 neutralizing antibody
Structural highlights
FunctionGLYCP_NIPAV Interacts with host ephrinB2/EFNB2 or ephrin B3/EFNB3 to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] [2] Publication Abstract from PubMedThe 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 beta1S2-beta1S3 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. A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.,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 Nat Commun. 2024 May 21;15(1):4330. doi: 10.1038/s41467-024-48601-w. PMID:38773072[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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