The Structure and Classification of Botulinum Toxins

Botulinum neurotoxins (BoNTs) are a family of bacterial protein toxins produced by various Clostridium species. They are traditionally classified into seven major serotypes (BoNT/A-G). Recent progress in sequencing microbial genomes has led to an ever-growing number of subtypes, chimeric toxins, BoNT-like toxins, and remotely related BoNT homologs, constituting an expanding BoNT superfamily. Recent structural studies of BoNTs, BoNT progenitor toxin complexes, tetanus neurotoxin (TeNT), toxin-receptor complexes, and toxin-substrate complexes have provided mechanistic understandings of toxin functions and the molecular basis for their variations. The growing BoNT superfamily of toxins present a natural repertoire that can be explored to develop novel therapeutic toxins, and the structural understanding of their variations provides a knowledge basis for engineering toxins to improve therapeutic efficacy and expand their clinical applications.