Insecticidal spider toxins are high affinity positive allosteric modulators of the nicotinic acetylcholine receptor
| Autor: | Penny Cutler, Yen-Hua Huang, Fergus Gerard Paul Earley, James A. Goodchild, Aurelien Bigot, Conan K. Wang, Davide Sabbadin, Chris Chambers, David J. Craik, Judith Blythe, Quentin Kaas |
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| Rok vydání: | 2019 |
| Předmět: |
Insecticides
Allosteric modulator Allosteric regulation Biophysics Spider Venoms Receptors Nicotinic Biochemistry Structure-Activity Relationship 03 medical and health sciences Allosteric Regulation Structural Biology Genetics medicine Animals Humans Receptor Molecular Biology 030304 developmental biology Acetylcholine receptor 0303 health sciences Chemistry 030302 biochemistry & molecular biology Cell Biology Spider toxin Nicotinic acetylcholine receptor Nicotinic agonist Acetylcholine medicine.drug |
| Zdroj: | FEBS Letters. 593:1336-1350 |
| ISSN: | 1873-3468 0014-5793 |
| Popis: | The insecticidal effects of ω-hexatoxin-Hv1a, κ-hexatoxin-Hv1c and ω/κ-hexatoxin-Hv1h are currently attributed to action at calcium and potassium channels. By characterizing the binding of these toxins to neuronal membranes, we show that they have more potent effects as positive allosteric modulators (PAMs) of insect nicotinic acetylcholine receptors (nAChRs), consistent with their neuroexcitatory toxicology. Alanine scanning analysis of ω-hexatoxin-Hv1a reveals a structure-activity relationship for binding that mirrors that for insecticidal activity. Spinosyn A does not compete with ω-hexatoxin-Hv-1a for binding, and we show that these two PAMs have distinct pharmacology of binding indicating that they act at different receptor populations. These toxins represent valuable tools for the characterization of insect nAChRs and for the development of more selective agrochemicals. |
| Databáze: | OpenAIRE |
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