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Structure paper

TitleStructure of the complete 14-subunit botulinum neurotoxin B complex reveals a unique anchoring through the narrow central pore of HA70.
Journal, issue, pagesSci Adv, Vol. 11, Issue 35, Page eadx5058, Year 2025
Publish dateAug 29, 2025
AuthorsAjda Krč / Sara Persson Košenina / Maria B Nowakowska / Geoffrey Masuyer / Pål Stenmark /
PubMed AbstractBotulinum 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 ...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.
External linksSci Adv / PubMed:40864696 / PubMed Central
MethodsEM (single particle)
Resolution2.49 - 3.67 Å
Structure data

EMDB-52460: M-PTC-HA70 complex from Botulinum neurotoxin Serotype B1
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-52461: M-PTC-HA70 complex from Botulinum neurotoxin Serotype B1
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-52476: M-PTC-HA70 complex from Botulinum neurotoxin Serotype B1
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-52666: M-PTC-HA70 complex from Botulinum neurotoxin Serotype B1
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-52672: NTNH-HA70 complex from Botulinum neurotoxin Serotype B1
Method: EM (single particle) / Resolution: 2.69 Å

EMDB-52681: NTNH-HA70 complex from Botulinum neurotoxin B1, focused map of HA70 trimer
Method: EM (single particle) / Resolution: 2.71 Å

EMDB-52686: NTNH-HA70 complex from Botulinum neurotoxin serotype B1, focused map of NTNH
Method: EM (single particle) / Resolution: 2.69 Å

EMDB-52732: HA70-HA17-HA33 complex from Botulinum neurotoxin serotype B1
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-52734: HA70-HA17-HA33 complex from Botulinum neurotoxin serotype B1, focused map of HA70 trimer
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-52735: HA70-HA17-HA33complex from Botulinum neurotoxin serotype B1, focused map of HA17-HA33 subcomplex
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-52739: L-PTC from Clostridium botulinum serotype B1, focused map of HA17-HA33 subcomplex (leg 1)
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-52740: L-PTC from Clostridium botulinum serotype B1, focused map of HA17-HA33 subcomplex (leg 2)
Method: EM (single particle) / Resolution: 3.38 Å

EMDB-52741: L-PTC from Clostridium botulinum serotype B1, focused map of HA17-HA33 subcomplex (leg 3)
Method: EM (single particle) / Resolution: 3.67 Å

EMDB-52742: L-PTC from Clostridium botulinum serotype B1, focused map of HA70 subcomplex
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-52743: L-PTC from Clostridium botulinum serotype B1, focused map of BoNT-NTNH subcomplex
Method: EM (single particle) / Resolution: 2.83 Å

EMDB-52763: Botulinum neurotoxin type B1 14-subunit Large Progenitor Toxin Complex (L-PTC)
Method: EM (single particle) / Resolution: 2.91 Å

53005

9qc7

EMDB-53005, PDB-9qc7:
BoNT-NTNH complex from Clostridium botulinum Serotype B1
Method: EM (single particle) / Resolution: 2.67 Å

53006

9qc8

EMDB-53006, PDB-9qc8:
BoNT-NTNH-HA70 complex from Clostridium botulinum Serotype B1
Method: EM (single particle) / Resolution: 2.9 Å

53010

9qce

EMDB-53010, PDB-9qce:
HA70-HA17-HA33 complex from Clostridium botulinum Serotype B1
Method: EM (single particle) / Resolution: 2.8 Å

53015

9qcm

EMDB-53015, PDB-9qcm:
Botulinum neurotoxin type B1, 14-subunit, Large Progenitor Toxin Complex (L-PTC)
Method: EM (single particle) / Resolution: 2.9 Å

53016

9qcn

EMDB-53016, PDB-9qcn:
HA70 complex from Clostridium botulinum Serotype B1
Method: EM (single particle) / Resolution: 2.49 Å

53017

9qco

EMDB-53017, PDB-9qco:
NTNH-HA70 complex from Clostridium botulinum Serotype B1
Method: EM (single particle) / Resolution: 2.76 Å

Source
  • clostridium botulinum (bacteria)
KeywordsTOXIN / progenitor-toxin complex / botulinum neurotoxin / hemagglutinin

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