A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1
文献类型:期刊论文
作者 | Yang SL1,2; Yang F3; Wei NN4; Hong J5; Li BW1,2; Luo L1,2; Rong MQ1; Yarov-Yarovoy V3; Zheng J[*]3; Wang KW[*]4,6,7 |
刊名 | NATURE COMMUNICATIONS
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出版日期 | 2015 |
卷号 | 6期号:X页码:e8297 |
通讯作者 | jzheng@ucdavis.edu ; wangkw@qdu.edu.cn ; rlai@mail.kiz.ac.cn |
合作状况 | 其它 |
英文摘要 | The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds to heat with exquisite sensitivity through an unknown mechanism. Here we report the identification of a novel toxin, RhTx, from the venom of the Chinese red-headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx is a 27-amino-acid small peptide that forms a compact polarized molecule with very rapid binding kinetics and high affinity for TRPV1. We show that RhTx targets the channel's heat activation machinery to cause powerful heat activation at body temperature. The RhTx-TRPV1 interaction is mediated by the toxin's highly charged C terminus, which associates tightly to the charge-rich outer pore region of the channel where it can directly interact with the pore helix and turret. These findings demonstrate that RhTx binding to the outer pore can induce TRPV1 heat activation, therefore providing crucial new structural information on the heat activation machinery. |
收录类别 | SCI |
资助信息 | This work was supported by funding from Ministry of Science and Technology of China (2013CB911300 and 2010CB529800), National Science Foundation of China (31025025, 31025025, U1132601 and 31200590), Chinese Academy of Sciences (KSZD-EW-Z-007) and Yunnan Province (2011CI139, 2012BC009) to R.L., Ministry of Science and Technology of China (2013CB531302), National Science Foundation of China (31370741), Ministry of Education of China, the 111 Project (B07001) to K.W.W., National Institutes of Health (R01NS072377) to J.Z. and American Heart Association (14POST19820027) to F.Y. |
语种 | 英语 |
源URL | [http://159.226.149.26:8080/handle/152453/9431] ![]() |
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.Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. 2.University of Chinese Academy of Sciences, Beijing 100009, China 3.Department of Physiology and Membrane Biology, University of California, Davis, California 95616, USA 4.Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China 5.College of Biological Science and Engineering, Fuzhou University, Fuzhou 350116, China 6.Department of Molecular and Cellular Pharmacology, PKU-IDG/McGovern Institute for Brain Research, Peking University School of Pharmaceutical Sciences, Beijing 100191, China 7.Department of Pharmacology, Qingdao University, Qingdao 266021, China |
推荐引用方式 GB/T 7714 | Yang SL,Yang F,Wei NN,et al. A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1[J]. NATURE COMMUNICATIONS,2015,6(X):e8297. |
APA | Yang SL.,Yang F.,Wei NN.,Hong J.,Li BW.,...&Lai R[*].(2015).A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1.NATURE COMMUNICATIONS,6(X),e8297. |
MLA | Yang SL,et al."A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1".NATURE COMMUNICATIONS 6.X(2015):e8297. |
入库方式: OAI收割
来源:昆明动物研究所
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