ジャーナル: Nat Commun / 年: 2024 タイトル: A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer. 著者: Pengfei Fan / Mengmeng Sun / Xinghai Zhang / Huajun Zhang / Yujiao Liu / Yanfeng Yao / Ming Li / Ting Fang / Bingjie Sun / Zhengshan Chen / Xiangyang Chi / Li Chen / Cheng Peng / Zhen Chen / ...著者: Pengfei Fan / Mengmeng Sun / Xinghai Zhang / Huajun Zhang / Yujiao Liu / Yanfeng Yao / Ming Li / Ting Fang / Bingjie Sun / Zhengshan Chen / Xiangyang Chi / Li Chen / Cheng Peng / Zhen Chen / Guanying Zhang / Yi Ren / Zixuan Liu / Yaohui Li / Jianmin Li / Entao Li / Wuxiang Guan / Shanshan Li / Rui Gong / Kaiming Zhang / Changming Yu / Sandra Chiu / 要旨: 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) ...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.
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E: Heavy chain of 1E5 Fab fragments F: Light chain of 1E5 Fab fragments A: Glycoprotein G C: Glycoprotein G G: Heavy chain of 1E5 Fab fragments H: Light chain of 1E5 Fab fragments B: Glycoprotein G D: Glycoprotein G
名称: Cryo-EM structure of conformation 1 of complex of Nipah virus attachment glycoprotein G with 1E5 neutralizing antibody タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES
分子量
単位: KILODALTONS/NANOMETER
由来(天然)
生物種: Nipah virus (ウイルス)
由来(組換発現)
生物種: Homo sapiens (ヒト)
緩衝液
pH: 8
試料
濃度: 0.16 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES