Structure of the complete 14-subunit botulinum neurotoxin B complex reveals a unique anchoring through the narrow central pore of HA70.
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Krč A, Košenina SP, Nowakowska MB, Masuyer G, Stenmark P
Sci Adv 11 (35) eadx5058 [2025-08-29; online 2025-08-27]
Botulinum neurotoxin serotype B1 (BoNT/B) is a highly potent neurotoxin and therapeutic agent. Here, we present the structure of the complete 14-subunit (780 kDa) progenitor toxin complex (L-PTC) and of five subcomplexes. The structures show how the toxin interacts with its associated components in their role to protect and deliver BoNT/B across epithelial barriers. Each subcomplex, including the M-PTC, M-PTC-HA70, NTNH-HA70, and HA70 trimer, provides detailed understanding of the assembly mechanism, in which the NTNH-nLoop adopts a unique fold that locks the M-PTC into a central pore formed by HA70. The HA subcomplex presents a tripod architecture with flexible legs that may adapt to the rugged cell surface. Mass photometry reveals the pH dependence of BoNT/B release from the complex which is unexpectedly influenced by the presence of HA70. This study provides the complete L-PTC structure, offering insights into its assemblage and supporting the development of countermeasures and therapeutic applications.
PubMed 40864696
DOI 10.1126/sciadv.adx5058
Crossref 10.1126/sciadv.adx5058