8SXP

Crystal structure of long neurotoxin from the venom of the king cobra (3FTx-L15) in complex with Fab of broadly neutralizing antibody 95Mat5

8SXP の概要

• エントリーDOI: 10.2210/pdb8sxp/pdb
• 分子名称: 95Mat5 Fab light chain, Long neurotoxin 2, 95Mat5 Fab heavy chain, ... (4 entities in total)
• 機能のキーワード: snake toxin, antibody, toxin, toxin-immune system complex, toxin/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 54709.01

構造登録者

Nguyen, T.K.Y. (登録日: 2023-05-23, 公開日: 2024-03-20, 最終更新日: 2024-11-13)

主引用文献

Khalek, I.S.,Senji Laxme, R.R.,Nguyen, Y.T.K.,Khochare, S.,Patel, R.N.,Woehl, J.,Smith, J.M.,Saye-Francisco, K.,Kim, Y.,Misson Mindrebo, L.,Tran, Q.,Kedzior, M.,Bore, E.,Limbo, O.,Verma, M.,Stanfield, R.L.,Menzies, S.K.,Ainsworth, S.,Harrison, R.A.,Burton, D.R.,Sok, D.,Wilson, I.A.,Casewell, N.R.,Sunagar, K.,Jardine, J.G.
Synthetic development of a broadly neutralizing antibody against snake venom long-chain neurotoxins
Sci Transl Med, 16:eadk1867-, 2024

PubMed Abstract: Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody-based universal antivenom to treat snakebite envenoming.

PubMed: 38381847
DOI: 10.1126/scitranslmed.adk1867

実験手法

X-RAY DIFFRACTION (2.9 Å)