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DOI | 10.1126/science.aaw2999 |
Molecular basis for pore blockade of human Na+ channel Na(v)1.2 by the mu-conotoxin KIIIA | |
Pan, Xiaojing1,2,3,4; Li, Zhangqiang1,2,3,4; Huang, Xiaoshuang1,2,3,4; Huang, Gaoxingyu1,2,3,4; Gao, Shuai5,7; Shen, Huaizong1,2,3,4; Liu, Lei2,3,5; Lei, Jianlin6; Yan, Nieng1,2,3,4,7 | |
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:1309-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA |
英文摘要 | The voltage-gated sodium channel Na(v)1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Na(v)1.2 bound to a peptidic pore blocker, the m-conotoxin KIIIA, in the presence of an auxiliary subunit, beta 2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of beta 2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Na(v)1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for 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:000462016400046 |
WOS关键词 | SODIUM-CHANNEL ; SAXITOXIN RECEPTOR ; AUXILIARY SUBUNIT ; RAT-BRAIN ; MUTATIONS ; TETRODOTOXIN ; EXPRESSION ; SPECTRUM ; FEBRILE ; BETA-3 |
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/201010 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Tsinghua Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China; 2.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China; 3.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Beijing 100084, Peoples R China; 4.Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China; 5.Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China; 6.Tsinghua Univ, Sch Life Sci, Technol Ctr Prot Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China; 7.Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA |
推荐引用方式 GB/T 7714 | Pan, Xiaojing,Li, Zhangqiang,Huang, Xiaoshuang,et al. Molecular basis for pore blockade of human Na+ channel Na(v)1.2 by the mu-conotoxin KIIIA[J]. SCIENCE,2019,363(6433):1309-+. |
APA | Pan, Xiaojing.,Li, Zhangqiang.,Huang, Xiaoshuang.,Huang, Gaoxingyu.,Gao, Shuai.,...&Yan, Nieng.(2019).Molecular basis for pore blockade of human Na+ channel Na(v)1.2 by the mu-conotoxin KIIIA.SCIENCE,363(6433),1309-+. |
MLA | Pan, Xiaojing,et al."Molecular basis for pore blockade of human Na+ channel Na(v)1.2 by the mu-conotoxin KIIIA".SCIENCE 363.6433(2019):1309-+. |
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