| Autor: |
Markel Martínez-Carranza, Jana Škerlová, Pyung-Gang Lee, Jie Zhang, Dave Burgin, Mark Elliott, Jules Philippe, Sarah Donald, Fraser Hornby, Linda Henriksson, Geoffrey Masuyer, Matthew Beard, Min Dong, Pål Stenmark |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
bioRxiv |
| Popis: |
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 at 3.1 Å resolution. 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 bothin vitroandin 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 weak ganglioside binding and exposed hydrophobic surfaces. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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