Characterization of a novel alpha4/4-conotoxin, Qc1.2, from vermivorous Conus quercinus.
Characterization of a novel alpha4/4-conotoxin, Qc1.2, from vermivorous Conus quercinus.
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DOI：
10.1093/abbs/gmp077
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发表时间：
2009-10
影响因子：
3.7
通讯作者：
C. Peng;Weihua Chen;Yuhong Han;T. Sanders;G. Chew;Jing Liu;E. Hawrot;C. Chi;Chunguang Wang
中科院分区：
文献类型：
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作者：
C. Peng;Weihua Chen;Yuhong Han;T. Sanders;G. Chew;Jing Liu;E. Hawrot;C. Chi;Chunguang Wang
作为新型α -conotoxin基因组织鉴定和克隆研究的一部分，本研究首次从中国南海采伐的Conus quercinus中克隆cDNA和基因组DNA，在一种蚓食性Conus物种中鉴定出α - 4/4-conotoxin，命名为Qc1.2。预测的Qc1.2成熟毒素含有14个氨基酸残基，在天然球形结构中具有两个二硫键（I-III， II-IV连接）。Qc1.2的成熟肽应该包含一个n端翻译后加工的焦谷氨酸残基和一个游离的羧基c端。该肽被化学合成并重新折叠以进一步表征其功能特性。合成的Qc1.2在水溶液中具有两个可相互转换的构象，这可能是由于其第一个Cys环中两个连续的Pro残基发生顺反异构化。利用爪蟾卵母细胞异种表达系统，Qc1.2可选择性低效抑制大鼠神经元α 3beta2和α 3beta4亚型烟碱乙酰胆碱受体。分别观察到约63%和37%的乙酰胆碱诱发电流被阻断，毒素迅速与受体分离。与其他表征的α - concontoxin成员相比，Qc1.2中赋予其受体识别谱的不寻常结构特征得到了解决。
As part of continuing studies of the identification of gene organization and cloning of novel alpha-conotoxins, the first alpha4/4-conotoxin identified in a vermivorous Conus species, designated Qc1.2, was originally obtained by cDNA and genomic DNA cloning from Conus quercinus collected in the South China Sea. The predicted mature toxin of Qc1.2 contains 14 amino acid residues with two disulfide bonds (I-III, II-IV connectivity) in a native globular configuration. The mature peptide of Qc1.2 is supposed to contain an N-terminal post-translationally processed pyroglutamate residue and a free carboxyl C-terminus. This peptide was chemically synthesized and refolded for further characterization of its functional properties. The synthetic Qc1.2 has two interconvertible conformations in aqueous solution, which may be due to the cis-trans isomerization of the two successive Pro residues in its first Cys loop. Using the Xenopus oocyte heterologous expression system, Qc1.2 was shown to selectively inhibit both rat neuronal alpha3beta2 and alpha3beta4 subtypes of nicotinic acetylcholine receptors with low potency. A block of about 63% and 37% of the ACh-evoked currents was observed, respectively, and the toxin dissociated rapidly from the receptors. Compared with other characterized alpha-conotoxin members, the unusual structural features in Qc1.2 that confer to its receptor recognition profile are addressed.