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DOI | 10.1126/science.aay3129 |
Cryo-EM structures of the human cation-chloride cotransporter KCC1 | |
Liu, Si1,2; Chang, Shenghai1,3; Han, Binming4; Xu, Lingyi1,5,6; Zhang, Mingfeng7; Zhao, Cheng1,7; Yang, Wei7; Wang, Feng8; Li, Jingyuan4; Delpire, Eric9; Ye, Sheng2,5,6; Bai, Xiao-chen10,11; Guo, Jiangtao1,7 | |
2019-10-25 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 366期号:6464页码:505-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA |
英文摘要 | Cation-chloride cotransporters (CCCs) mediate the coupled, electroneutral symport of cations with chloride across the plasma membrane and are vital for cell volume regulation, salt reabsorption in the kidney, and gamma-aminobutyric acid (GABA)-mediated modulation in neurons. Here we present cryo-electron microscopy (cryo-EM) structures of human potassium-chloride cotransporter KCC1 in potassium chloride or sodium chloride at 2.9- to 3.5-angstrom resolution. KCC1 exists as a dimer, with both extracellular and transmembrane domains involved in dimerization. The structural and functional analyses, along with computational studies, reveal one potassium site and two chloride sites in KCC1, which are all required for the ion transport activity. KCC1 adopts an inward-facing conformation, with the extracellular gate occluded. The KCC1 structures allow us to model a potential ion transport mechanism in KCCs and provide a blueprint for drug design. |
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:000493177900050 |
WOS关键词 | X-RAY-STRUCTURE ; CL-COTRANSPORT ; HYPOKALEMIC ALKALOSIS ; MOLECULAR PHYSIOLOGY ; BARTTERS-SYNDROME ; CRYSTAL-STRUCTURE ; MUTATIONS ; STOICHIOMETRY ; VALIDATION ; PROTEINS |
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/202634 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Biophys,Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China; 2.Tianjin Univ, Sch Life Sci, Tianjin Key Lab Funct & Applicat Biol Macromol St, 92 Weijin Rd, Tianjin 300072, Peoples R China; 3.Zhejiang Univ, Sch Med, Ctr Cryoelect Microscopy, Hangzhou 310058, Zhejiang, Peoples R China; 4.Zhejiang Univ, Inst Quantitat Biol, Dept Phys, Zhejiang Prov Key Lab Quantum Technol & Device, Hangzhou 310027, Zhejiang, Peoples R China; 5.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China; 6.Zhejiang Univ, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Zhejiang, Peoples R China; 7.Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Dept Biophys,Inst Neurosci, Hangzhou 310058, Zhejiang, Peoples R China; 8.Wuxi Biortus Biosci Co Ltd, 6 Dongsheng West Rd, Jiangyin 214437, Peoples R China; 9.Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA; 10.Univ Texas Southwestern Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA; 11.Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA |
推荐引用方式 GB/T 7714 | Liu, Si,Chang, Shenghai,Han, Binming,et al. Cryo-EM structures of the human cation-chloride cotransporter KCC1[J]. SCIENCE,2019,366(6464):505-+. |
APA | Liu, Si.,Chang, Shenghai.,Han, Binming.,Xu, Lingyi.,Zhang, Mingfeng.,...&Guo, Jiangtao.(2019).Cryo-EM structures of the human cation-chloride cotransporter KCC1.SCIENCE,366(6464),505-+. |
MLA | Liu, Si,et al."Cryo-EM structures of the human cation-chloride cotransporter KCC1".SCIENCE 366.6464(2019):505-+. |
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