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Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2008 May 23; Vol. 283 (21), pp. 14571-80. Date of Electronic Publication: 2008 Apr 01. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Animals
Chromatography, Gel
Chromatography, High Pressure Liquid
Circular Dichroism
Cobra Neurotoxin Proteins isolation & purification
Dimerization
Elapidae
Humans
Models, Molecular
Protein Structure, Tertiary
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Cobra Neurotoxin Proteins chemistry
Cobra Neurotoxin Proteins metabolism
Disulfides chemistry
Disulfides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 283
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18381281
- Full Text :
- https://doi.org/10.1074/jbc.M802085200