Characterization of a novel alpha4/4-conotoxin,Qc1.2,from vermivorous Conus quercinus
作者单位:Department of Molecular PharmacologyPhysiology and BiotechnologyBrown Medical SchoolProvidenceRhode Island 02912USA
会议名称:《第九届中国生物毒素学术研讨会》
会议日期:2009年
学科分类:100405[医学-卫生毒理学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 10[医学]
关 键 词:nicotinic acetylcholine receptor subtypes α4/4-conotoxins posttranslational modification Xenopus oocytes
摘 要:正Theα4/4-conotoxin first identified in a vermivorous Conus speices, designated Qc1.2,was originally obtained by cDNA and genomic DNA cloning from Conus quercinus collected in the South China *** predicted mature toxin of Qc1.2 contains 14 amino acid residues with two disulfide bonds(Ⅰ-Ⅲ,Ⅱ-Ⅳconnectivity) in a native globular *** mature peptide of Qc1.2 is supposed to contain an N-terminal posttranslationally processed pyroglutamate residue and a free carboxyl *** peptide was chemically synthesized and refolded for further characterizing its function *** synthetic Qc1.2 has two interconvertible conformations in aqueous solution,which may due to the cis-trans isomerization of the two successive Pro residues in its first cysteine *** the Xenopus oocyte heterologous expression system,Qc1.2 was shown to selectively inhibit both rat neuronalα3β2 andα3β4 subtypes of nicotinic acetylcholine receptors with low potency.A block of approximately 63%and 37%of the ACh-evoked currents was observed,respectively,and the toxin dissociated rapidly from the *** to other characterizedα-conotoxin members,the unusual structural features in Qc1.2 that confer to its receptor recognition profile are addressed.