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| Title | Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein. |
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| Journal, issue, pages | Commun Chem, Vol. 7, Issue 1, Page 179, Year 2024 |
| Publish date | Aug 13, 2024 |
Authors | Markel Martínez-Carranza / Jana Škerlová / Pyung-Gang Lee / Jie Zhang / Ajda Krč / Abhishek Sirohiwal / Dave Burgin / Mark Elliott / Jules Philippe / Sarah Donald / Fraser Hornby / Linda Henriksson / Geoffrey Masuyer / Ville R I Kaila / Matthew Beard / Min Dong / Pål Stenmark / ![]() |
| PubMed Abstract | Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein ...Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces. |
External links | Commun Chem / PubMed:39138288 / PubMed Central |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 3.12 - 3.3 Å |
| Structure data | EMDB-16330, PDB-8byp: ![]() PDB-8qft: |
| Source |
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Keywords | TOXIN / Botulinum neurotoxin / botulism / progenitor toxin complex / Clostridium botulinum / strain 111 |
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