Characterization of a T-superfamily conotoxin TxVC from Conus textile that selectively targets neuronal nAChR subtypes
| Autor: | Ying Wu, Ling Jiang, Qiuyun Dai, Jiuping Ding, Zhuguo Liu, Tianpeng Du, Sheng Wang, Shuo Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular BK channel Conus textile Protein Conformation Xenopus Biophysics Receptors Nicotinic complex mixtures Biochemistry Animals Humans Amino Acid Sequence Conotoxin Nuclear Magnetic Resonance Biomolecular Molecular Biology Cells Cultured Neurons Binding Sites biology Chemistry Sodium channel Calcium channel HEK 293 cells Conus Snail Cell Biology biology.organism_classification Recombinant Proteins Nicotinic acetylcholine receptor HEK293 Cells nervous system Oocytes biology.protein Female Pharmacophore Conotoxins |
| Zdroj: | Biochemical and Biophysical Research Communications. 454:151-156 |
| ISSN: | 0006-291X |
| Popis: | T-superfamily conotoxins have a typical cysteine pattern of "CC-CC", and are known to mainly target calcium or sodium ion channels. Recently, we screened the targets of a series of T-superfamily conotoxins and found that a new T-superfamily conotoxin TxVC (KPCCSIHDNSCCGL-NH2) from the venom of Conus textile. It selectively targeted the neuronal nicotinic acetylcholine receptor (nAChR) subtypes alpha 4 beta 2 and alpha 3 beta 2, with IC50 values of 343.4 and 1047.2 nM, respectively, but did not exhibit obvious pharmacological effects on voltage-gated potassium, sodium or calcium channel in DRG cells, the BK channels expressed in HEK293 cells, or the Kv channels in L beta T2 cells. The changes in the inhibitory activities of its Ala mutants, the NMR structure, and molecular simulation results based on other conotoxins targeting nAChR alpha 4 beta 2, all demonstrated that the residues Ile(6) and Leu(14) were the main hydrophobic pharmacophores. To our best knowledge, this is the first T-superfamily conotoxin that inhibits neuronal nAChRs and possesses high binding affinity to alpha 4 beta 2. This finding will expand the knowledge of the targets of T-superfamily conotoxins and the motif information could help the design of new nAChR inhibitors. (C) 2014 Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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