Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex
- Cornell
Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- FOREIGNNIHNIAID
- OSTI ID:
- 1035706
- Journal Information:
- Science, Journal Name: Science Journal Issue: 02, 2012 Vol. 335; ISSN SCIEAS; ISSN 0036-8075
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a structural topology similar to bactericidal/permeability-increasing protein
Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1
Journal Article
·
Sun Oct 15 20:00:00 EDT 2017
· Toxicon
·
OSTI ID:1434740
Crystal structures of OrfX1, OrfX2 and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1
Journal Article
·
Tue Jan 17 19:00:00 EST 2023
· FEBS Letters
·
OSTI ID:2423355