8XPY

Structure of Nipah virus Malaysia string G protein ectodomain monomer bound to single-domain antibody n425 at 3.63 Angstroms overall resolution

8XPY の概要

• エントリーDOI: 10.2210/pdb8xpy/pdb
• EMDBエントリー: 38563
• 分子名称: Glycoprotein G, single-domain antibody n425, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: antibody, viral protein
• 由来する生物種: Henipavirus nipahense; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84422.95

構造登録者

Sun, L.,Chen, Z.,Sun, Y.,Mao, Q. (登録日: 2024-01-04, 公開日: 2024-09-18, 最終更新日: 2025-06-25)

主引用文献

Wang, Y.,Sun, Y.,Shen, Z.,Wang, C.,Qian, J.,Mao, Q.,Wang, Y.,Song, W.,Kong, Y.,Zhan, C.,Chen, Z.,Dimitrov, D.S.,Yang, Z.,Jiang, S.,Wu, F.,Lu, L.,Ying, T.,Sun, L.,Wu, Y.
Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.
Nat Commun, 15:6892-6892, 2024

PubMed Abstract: Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.

PubMed: 39134522
DOI: 10.1038/s41467-024-51066-6

実験手法

ELECTRON MICROSCOPY (3.63 Å)