Engineered Conotoxin Differentially Blocks and Discriminates Rat and Human α7 Nicotinic Acetylcholine Receptors
Shuai Wang, Xiaopeng Zhu, Manqi Zhangsun, Yong Wu, Jinpeng Yu, Peta J. Harvey, Quentin Kaas, Dongting Zhangsun, David J. Craik, Sulan Luo
Abstract
: 97 nM). Substitutions between rat and human α7 nAChRs at three key mutation sites revealed that no single mutant could completely change the activity profile of amidated [Q1G,ΔR14]LvIB. Rather, we found that the combined influence of Gln141, Asn184, and Lys186 determines the α7 nAChR species specificity of this peptide. This engineered α4/4 conotoxin has potential applications as a template for designing ligands to selectively block human α7 nAChRs.
Topics & Concepts
ChemistryNicotinic agonistAcetylcholine receptorConotoxinNicotinic acetylcholine receptorMutantReceptorAcetylcholineStereochemistryPeptideBiochemistryPharmacologyBiologyGeneNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and SignalingIon channel regulation and function