High resolution crystal structures of Clostridium botulinum neurotoxin A3 and A4 binding domains

Abstract

Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening condition, botulism. However, while they have the potential to cause serious harm, they are increasingly being utilised for therapeutic applications. BoNTs comprise of seven distinct serotypes termed BoNT/A through BoNT/G, with the most widely characterised being sub-serotype BoNT/A1. Each BoNT consists of three structurally distinct domains, a binding domain (H_C), a translocation domain (H_N), and a proteolytic domain (LC). The H_C domain is responsible for the highly specific targeting of the neurotoxin to neuronal cell membranes. Here, we present two high-resolution structures of the binding domain of subtype BoNT/A3 (H_C/A3) and BoNT/A4 (H_C/A4) at 1.6 Å and 1.34 Å resolution, respectively. The structures of both proteins share a high degree of similarity to other known BoNT H_C domains whilst containing some subtle differences, and are of benefit to research into therapeutic neurotoxins with novel characteristics.

Keywords: Binding domain structure; Botulinum neurotoxin; Clostridium botulinum; Crystallography; Subtypes.