A nut-and-bolt assembly of the bimodular large progenitor botulinum neurotoxin complex.

ABSTRACT: Botulinum neurotoxin serotype A (BoNT/A) is naturally produced by bacteria along with four nontoxic neurotoxin-associated proteins (NTNH, HA70, HA33, and HA17), forming a bimodular large progenitor toxin complex (L-PTC). The BoNT/A-NTNH complex protects the toxin from adverse environment, while the complex consisting of HA proteins facilitates toxin absorption during oral intoxication. How these two independent modules assemble into the L-PTC remains unclear. Here, we report the crystal structure of the BoNT/A-NTNH-HA70 complex at ~2.9-Å resolution. The structure reveals that the BoNT/A-NTNH complex is anchored into a concentric double β-barrel channel of trimeric HA70 through a short β-hairpin of NTNH (termed nLoop), resembling a nut-and-bolt attachment. We find that the nLoop of NTNH is

SUBMITTER: Lam KH 

PROVIDER: S-EPMC12383247 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature