High‐resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6

Clostridium botulinum neurotoxins (BoNTs) cause flaccid paralysis through inhibition of acetylcholine release from motor neurons; however, at tiny doses, this property is exploited for use as a therapeutic. Each member of the BoNT family of proteins consists of three distinct domains: a binding domain that targets neuronal cell membranes (H(C)), a translocation domain (H(N)) and a catalytic domain (LC). Here, we present high‐resolution crystal structures of the binding domains of BoNT subtypes/A5 (H(C)/A5) and/A6 (H(C)/A6). These structures show that the core fold identified in other subtypes is maintained, but with subtle differences at the expected receptor‐binding sites.