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

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.