A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit | |
Sun PB1; Wu FM2; Wen M1; Yang XW3; Wang Cy1; Li YM4; He SF5; Zhang LH[*]1; Zhang Y[*]3; Tian CL[*]1,2 | |
刊名 | SCIENTIFIC REPORTS
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2015 | |
卷号 | 5期号:X页码:e13399 |
通讯作者 | zlhustc@ustc.edu.cn ; zhangy@mail.kiz.ac.cn ; cltian@ustc.edu.cn |
合作状况 | 其它 |
英文摘要 | KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes. |
收录类别 | SCI |
资助信息 | The work is supported by the Ministry of Science and Technology of China 2015CB910103 for C.T. and 2012CB910200 for F.W., and National Natural Science Foundation of China grant U1332138, no.31100563 and no.31100847, and the Fundamental Research Funds for the Central Universities of China (WK2070000033). |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://159.226.149.26:8080/handle/152453/9450] ![]() |
专题 | 昆明动物研究所_动物活性蛋白多肽组学 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.Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, P. R. China 2.High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, P.R. China 3.Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan P.R. China 4.School of Medical Engineering, Hefei University of Technology, Hefei, P. R. China 5.Department of anesthesiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, P. R. China |
推荐引用方式 GB/T 7714 | Sun PB,Wu FM,Wen M,et al. A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit[J]. SCIENTIFIC REPORTS,2015,5(X):e13399. |
APA | Sun PB.,Wu FM.,Wen M.,Yang XW.,Wang Cy.,...&Tian CL[*].(2015).A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit.SCIENTIFIC REPORTS,5(X),e13399. |
MLA | Sun PB,et al."A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit".SCIENTIFIC REPORTS 5.X(2015):e13399. |
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