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DOI | 10.1126/science.aav8573 |
Structural basis of alpha-scorpion toxin action on Na-v channels | |
Clairfeuille, Thomas1; Cloake, Alexander1,2; Infield, Daniel T.3; Llongueras, Jose P.4; Arthur, Christopher P.1; Li, Zhong Rong5; Jian, Yuwen6; Martin-Eauclaire, Marie-France7; Bougis, Pierre E.7; Ciferri, Claudio1; Ahern, Christopher A.3; Bosmans, Frank8; Hackos, David H.6; Rohou, Alexis1; Payandeh, Jian1 | |
2019-03-22 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 363期号:6433页码:1302-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; England; France; Belgium |
英文摘要 | Fast inactivation of voltage-gated sodium (Na-v) channels is essential for electrical signaling, but its mechanism remains poorly understood. Here we determined the structures of a eukaryotic Na-v channel alone and in complex with a lethal alpha-scorpion toxin, AaH2, by electron microscopy, both at 3.5-angstrom resolution. AaH2 wedges into voltage-sensing domain IV (VSD4) to impede fast activation by trapping a deactivated state in which gating charge interactions bridge to the acidic intracellular carboxyl-terminal domain. In the absence of AaH2, the S4 helix of VSD4 undergoes a similar to 13-angstrom translation to unlatch the intracellular fast-inactivation gating machinery. Highlighting the polypharmacology of alpha-scorpion toxins, AaH2 also targets an unanticipated receptor site on VSD1 and a pore glycan adjacent to VSD4. Overall, this work provides key insights into fast inactivation, electromechanical coupling, and pathogenic mutations in Na-v channels. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000462016400044 |
WOS关键词 | GATED SODIUM-CHANNELS ; FUNCTIONAL EXPRESSION ; RECEPTOR-SITE ; DOMAIN IV ; LONG-QT ; MOLECULAR DETERMINANTS ; FAST INACTIVATION ; SKELETAL-MUSCLE ; IONIC CURRENTS ; VENOM PEPTIDES |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201017 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Genentech Inc, Dept Struct Biol, San Francisco, CA 94080 USA; 2.Univ Oxford, Dept Phys, Oxford OX1 3PU, England; 3.Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA; 4.Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA; 5.Genentech Inc, Dept Biomol Resources, San Francisco, CA 94080 USA; 6.Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA; 7.Aix Marseille Univ, CNRS, LNC, UMR 7291, F-13003 Marseille, France; 8.Univ Ghent, Dept Basic & Appl Med Sci, B-9000 Ghent, Belgium |
推荐引用方式 GB/T 7714 | Clairfeuille, Thomas,Cloake, Alexander,Infield, Daniel T.,et al. Structural basis of alpha-scorpion toxin action on Na-v channels[J]. SCIENCE,2019,363(6433):1302-+. |
APA | Clairfeuille, Thomas.,Cloake, Alexander.,Infield, Daniel T..,Llongueras, Jose P..,Arthur, Christopher P..,...&Payandeh, Jian.(2019).Structural basis of alpha-scorpion toxin action on Na-v channels.SCIENCE,363(6433),1302-+. |
MLA | Clairfeuille, Thomas,et al."Structural basis of alpha-scorpion toxin action on Na-v channels".SCIENCE 363.6433(2019):1302-+. |
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