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Solution Conformation of alpha-conotoxin PIA
Structural highlights
FunctionCA1A_CONPU Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks nAChR (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > alpha-3/beta-4). Does not block the muscle nor the major neuronal nAChR alpha-4/beta-2. Discriminates between nAChRs containing alpha-6 and alpha-3 subunits, being selective for alpha-6.[1] Publication Abstract from PubMedalpha-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR) antagonist isolated from Conus purpurascens that targets nAChR subtypes containing alpha6 and alpha3 subunits. alpha-conotoxin PIA displays 75-fold higher affinity for rat alpha6/alpha3beta2beta3 nAChRs than for rat alpha3beta2 nAChRs. We have determined the three-dimensional structure of alpha-conotoxin PIA by nuclear magnetic resonance spectroscopy. The alpha-conotoxin PIA has an "omega-shaped" overall topology as other alpha4/7 subfamily conotoxins. Yet, unlike other neuronally targeted alpha4/7-conotoxins, its N-terminal tail Arg1-Asp2-Pro3 protrudes out of its main molecular body because Asp2-Pro3-Cys4-Cys5 forms a stable type I beta-turn. In addition, a kink introduced by Pro15 in the second loop of this toxin provides a distinct steric and electrostatic environment from those in alpha-conotoxins MII and GIC. By comparing the structure of alpha-conotoxin PIA with other functionally related alpha-conotoxins we suggest structural features in alpha-conotoxin PIA that may be associated with its unique receptor recognition profile. Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6 subunit containing nicotinic acetylcholine receptors.,Chi SW, Lee SH, Kim DH, Kim JS, Olivera BM, McIntosh JM, Han KH Biochem Biophys Res Commun. 2005 Dec 30;338(4):1990-7. Epub 2005 Nov 7. PMID:16289101[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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