Structural highlights
Publication Abstract from PubMedAlpha6beta2 nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons in the CNS are potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine addiction and Parkinson's disease. However, recent studies indicate that the alpha6 subunit can also associate with the beta4 subunit to form alpha6beta4 nAChRs that are difficult to pharmacologically distinguish from alpha6beta2, alpha3beta4 and alpha3beta2 subtypes. The current study characterized a novel 16 amino acid alpha-conotoxin (alpha-CTx) TxIB from Conus textile whose sequence is GCCSDPPCRNKHPDLC-amide as deduced from gene cloning. The peptide and an analog with an additional C-terminal glycine were chemically synthesized and tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes. alpha-CTx TxIB blocked alpha6/alpha3beta2beta3 nAChR with an IC50 of 28 nM. In contrast, the peptide showed little or no block of other tested subtypes at concentrations up to 10 muM. The three-dimensional solution structure of alpha-CTx TxIB was determined using NMR spectroscopy. alpha-CTx TxIB represents a uniquely selective ligand for probing the structure and function of alpha6beta2 nAChRs. Characterization of a Novel alpha-Conotoxin from Conus textile that Selectively Targets Alpha6/alpha3beta2betab3 Nicotinic Acetylcholine Receptors.,Luo S, Zhangsun D, Wu Y, Zhu X, Hu Y, McIntyre M, Christensen S, Akcan M, Craik DJ, McIntosh JM J Biol Chem. 2012 Nov 26. PMID:23184959[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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