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Characterization of a Novel Alpha4/6-Conotoxin TxIC from Conus textile that Potently Blocks alpha3beta4 Nicotinic Acetylcholine ReceptorsCharacterization of a Novel Alpha4/6-Conotoxin TxIC from Conus textile that Potently Blocks alpha3beta4 Nicotinic Acetylcholine Receptors
Structural highlights
FunctionCA112_CONLI Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin inhibits alpha-3-beta-4, alpha-6/alpha-3-beta-4, and alpha-2-beta-4 nAChRs.[UniProtKB:K8DWB5] Publication Abstract from PubMedThe alpha3beta4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an alpha-4/6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds. TxID was synthesized using solid phase methods, and the synthetic peptide was functionally tested on nAChRs heterologously expressed in Xenopus laevis oocytes. TxID blocked rat alpha3beta4 nAChRs with a 12.5 nM IC50, which places it among the most potent alpha3beta4 nAChR antagonists. TxID also blocked the closely related alpha6/alpha3beta4 with a 94 nM IC50 but showed little activity on other nAChR subtypes. NMR analysis showed that two major structural isomers exist in solution, one of which adopts a regular alpha-CTx fold but with different surface charge distribution to other 4/6 family members. alpha-CTx TxID is a novel tool with which to probe the structure and function of alpha3beta4 nAChRs. Characterization of a Novel alpha-Conotoxin TxID from Conus textile That Potently Blocks Rat alpha3beta4 Nicotinic Acetylcholine Receptors.,Luo S, Zhangsun D, Zhu X, Wu Y, Hu Y, Christensen S, Harvey PJ, Akcan M, Craik DJ, McIntosh JM J Med Chem. 2013 Nov 22. PMID:24200193[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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