Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel

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	Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel
	Rong MQ 1,2; Duan ZG 1; Chen JL 1; Li JL 1; Xiao YC 1; Liang SP[*]1
刊名	PLOS ONE
	2013
卷号	6 期号:8 页码:e65984
通讯作者	liangsp@hunnu.edu.cn
合作状况	其它
英文摘要	Huwentoxin-IV (HWTX-IV), a tetrodotoxin-sensitive (TTX-s) sodium channel antagonist, is found in the venom of the Chinese spider Ornithoctonus huwena. A naturally modified HWTX-IV (mHWTX-IV), having a molecular mass 18 Da lower than HWTX-IV, has also been isolated from the venom of the same spider. By a combination of enzymatic fragmentation and MS/MS de novo sequencing, mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid replaced by pyroglutamic acid. mHWTX-IV inhibited tetrodotoxin-sensitive voltage-gated sodium channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV. mHWTX-IV showed the same activation and inactivation kinetics seen for native HWTX-IV. In contrast with HWTX-IV, which dissociates at moderate voltage depolarization voltages (+50 mV, 180000 ms), mHWTX-IV inhibition of TTX-sensitive sodium channels is not reversed by strong depolarization voltages (+200 mV, 500 ms). Recovery of Nav1.7current was voltage-dependent and was induced by extreme depolarization in the presence of HWTX-IV, but no obvious current was elicited after application of mHWTX-IV. Our data indicate that the N-terminal modification of HWTX-IV gives the peptide toxin a greater ability to trap the voltage sensor in the sodium channel. Loss of a negative charge, caused by cyclization at the N-terminus, is a possible reason why the modified toxin binds much stronger. To our knowledge, this is the first report of a pyroglutamic acid residue in a spider toxin; this modification seems to increase the trapping ability of the voltage sensor in the sodium channel.
收录类别	SCI
资助信息	This work was supported by grants from the National 973 Project of China (2010CB529801, 2009BC526510), the Science Research Fund of the Hunan Provincial Education Department (10B049), the National Natural Science Foundation of China (31200590, 30900242), the National Natural Science Foundation of China (grant 3100047), the Hunan Education Department of Science and Technology Research Project (10C0961).
语种	英语
WOS记录号	WOS:000321738400008
公开日期	2013-12-13
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7725]
专题	昆明动物研究所_动物毒素室昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
推荐引用方式 GB/T 7714	Rong MQ,Duan ZG,Chen JL,et al. Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel[J]. PLOS ONE,2013,6(8):e65984.
APA	Rong MQ,Duan ZG,Chen JL,Li JL,Xiao YC,&Liang SP[*].(2013).Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel.PLOS ONE,6(8),e65984.
MLA	Rong MQ,et al."Native Pyroglutamation of Huwentoxin-IV: A Post-Translational Modification that Increases the Trapping Ability to the Sodium Channel".PLOS ONE 6.8(2013):e65984.