| Autor: |
Alexey V, Osipov, Igor E, Kasheverov, Yana V, Makarova, Vladislav G, Starkov, Olga V, Vorontsova, Rustam Kh, Ziganshin, Tatyana V, Andreeva, Marina V, Serebryakova, Audrey, Benoit, Ronald C, Hogg, Daniel, Bertrand, Victor I, Tsetlin, Yuri N, Utkin |
| Rok vydání: |
2008 |
| Předmět: |
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| Zdroj: |
The Journal of biological chemistry. 283(21) |
| ISSN: |
0021-9258 |
| Popis: |
Disulfide-bound dimers of three-fingered toxins have been discovered in the Naja kaouthia cobra venom; that is, the homodimer of alpha-cobratoxin (a long-chain alpha-neurotoxin) and heterodimers formed by alpha-cobratoxin with different cytotoxins. According to circular dichroism measurements, toxins in dimers retain in general their three-fingered folding. The functionally important disulfide 26-30 in polypeptide loop II of alpha-cobratoxin moiety remains intact in both types of dimers. Biological activity studies showed that cytotoxins within dimers completely lose their cytotoxicity. However, the dimers retain most of the alpha-cobratoxin capacity to compete with alpha-bungarotoxin for binding to Torpedo and alpha7 nicotinic acetylcholine receptors (nAChRs) as well as to Lymnea stagnalis acetylcholine-binding protein. Electrophysiological experiments on neuronal nAChRs expressed in Xenopus oocytes have shown that alpha-cobratoxin dimer not only interacts with alpha7 nAChR but, in contrast to alpha-cobratoxin monomer, also blocks alpha3beta2 nAChR. In the latter activity it resembles kappa-bungarotoxin, a dimer with no disulfides between monomers. These results demonstrate that dimerization is essential for the interaction of three-fingered neurotoxins with heteromeric alpha3beta2 nAChRs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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