一种具有增强河豚毒素敏感性钠电流能力的新型M超家族芋螺毒素的鉴定。

Identification of a novel M-superfamily conotoxin with the ability to enhance tetrodotoxin sensitive sodium currents.

作者信息

Wang Lei, Liu Junliang, Pi Canhui, Zeng Xiayun, Zhou Maojun, Jiang Xiaoyu, Chen Shangwu, Ren Zhenghua, Xu Anlong

机构信息

State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 Xingangxi Road, 510275 Guangzhou, People's Republic of China.

出版信息

Arch Toxicol. 2009 Oct;83(10):925-32. doi: 10.1007/s00204-009-0453-8. Epub 2009 Jun 27.

DOI:10.1007/s00204-009-0453-8

PMID:19562324

Abstract

In this work, a novel M-superfamily conotoxin, designated lt3a, was purified from the crude venom of Conus litteratus. Combined with peptide sequencing, MALDI-TOF mass spectrometry and cDNA cloning techniques, the amino acid sequence of lt3a was supposed to be DgammaCCgamma OQWCDGACDCCS, where O is hydroxyproline and gamma is carboxyglutamate. The Cys framework of lt3a (-CC-C-C-CC-) is similar to that of psi-, mu-, kappaM-conotoxins, which are representatives of M-conotoxins. Peptide lt3a is categorized into M1 branch based on the number of residues in the last Cys loop. Whole cell patch-clamp study on adult rat dorsal root ganglion neurons indicated that lt3a could enhance tetrodotoxin-sensitive sodium currents. This is a previously unknown function of M-superfamily conotoxins.

摘要

在本研究中，从织锦芋螺的粗毒液中纯化出一种新型的M超家族芋螺毒素，命名为lt3a。结合肽测序、基质辅助激光解吸电离飞行时间质谱和cDNA克隆技术，推测lt3a的氨基酸序列为DγCCγOQWCDGACDCCS，其中O为羟脯氨酸，γ为羧基谷氨酸。lt3a的半胱氨酸框架（-CC-C-C-CC-）与psi-、mu-、kappaM-芋螺毒素相似，它们是M-芋螺毒素的代表。根据最后一个半胱氨酸环中的残基数，肽lt3a被归类为M1分支。对成年大鼠背根神经节神经元进行的全细胞膜片钳研究表明，lt3a可增强河豚毒素敏感的钠电流。这是M超家族芋螺毒素以前未知的功能。