不同血清型肉毒毒素受体结合域研究进展

Research progress in receptor-binding domains of different serotypes of botulinum neurotoxins

摘要:

肉毒毒素(botulinum neurotoxin, BoNT)是人类已知毒性最强的蛋白质之一，可以引起肌肉松弛麻痹，严重时可导致死亡。肉毒毒素共分为7种血清型(BoNT/A-BoNT/G)，根据氨基酸序列差异可进一步分为40多种亚型。肉毒毒素分子结构由3个基本结构域组成：重链羧基端细胞受体结合域、氨基端的易位域和轻链催化域。在运动神经元表面，受体结合域首先与聚唾液酸神经节苷脂结合，随后与突触囊泡蛋白2或突触囊泡结合蛋白结合形成双受体复合物。每种血清型的受体结合域都必须与其相应受体结合才能发挥作用。肉毒毒素的结构功能及其对宿主的作用一直都是研究热点。近年来，因受体结合域可以促进肉毒毒素与运动神经元膜特异性结合，而成为新的研究方向。本综述将概述不同血清型肉毒毒素与受体结合过程中受体结合域结构变化和结合位点差异。通过分析不同血清型及亚型的序列以及受体结合域结构特征，可以更好地了解细胞受体结合域的序列差异和功能，并为肉毒毒素的治疗策略提供新思路。

Abstract:

Botulinum neurotoxins (BoNTs), a group of the most toxic proteins, can cause muscle paralysis and even lead to death in severe cases. BoNTs can be classified into 7 serotypes (BoNT/A-BoNT/G) and further classified into more than 40 subtypes according to the differences in amino acid sequences. BoNTs consist of three basic domains: the C-terminal receptor-binding domain of the heavy chain, the N-terminal translocation domain, and the light-chain catalytic domain. On the surface of motor neurons, the receptor-binding domain binds first to polysialoganglioside and subsequently to synaptic vesicle protein 2 or synaptotagmin to form a two-receptor complex. The functioning of each serotype relies on the binding of the receptor-binding domain to the corresponding receptor. BoNTs have always been a research hotspot in terms of the structure, function, and effect on the host. The role of the receptor-binding domain in promoting the specific binding of BoNTs to motor neurons has become a new research direction. This review summarizes the structural changes of the receptor-binding domains and the differences in binding sites during the binding of different serotypes of BoNTs to receptors. By analyzing the sequences and structural characteristics of the receptor-binding domains of different serotypes and subtypes, we can fully understand the sequence differences and functions of the receptor-binding domain and give insights into the treatment of BoNTs.