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DOI | 10.1126/science.aav7942 |
Structure and dynamics of the active human parathyroid hormone receptor-1 | |
Zhao, Li-Hua1; Ma, Shanshan1,2; Sutkeviciute, Ieva3; Shen, Dan-Dan4,5; Zhou, X. Edward6; de Waal, Parker W.6; Li, Chen-Yao1,2; Kang, Yanyong1; Clark, Lisa J.3,7; Jean-Alphonse, Frederic G.3; White, Alex D.3,8; Yang, Dehua1; Dai, Antao1; Cai, Xiaoqing1; Chen, Jian9; Li, Cong9; Jiang, Yi1; Watanabe, Tomoyuki10,11,12; Gardella, Thomas J.10,11; Melcher, Karsten6; Wang, Ming-Wei1,9; Vilardaga, Jean-Pierre3; Xu, H. Eric1,6; Zhang, Yan4,5 | |
2019-04-12 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6436页码:148-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA; Japan |
英文摘要 | The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation. |
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:000464620000035 |
WOS关键词 | CRYO-EM STRUCTURE ; GLP-1 RECEPTOR ; PTHRP RECEPTOR ; BINDING ; ACTIVATION ; RECOGNITION ; VALIDATION ; MECHANISM ; RESPONSES ; DOMAINS |
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/201192 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA; 4.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China; 5.Zhejiang Univ, Sch Med, Dept Biophys, Hangzhou 310058, Zhejiang, Peoples R China; 6.Van Andel Res Inst, Innovat & Integrat Program, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA; 7.Univ Pittsburgh, Sch Med, Grad Program Mol Biophys & Struct Biol, Pittsburgh, PA 15261 USA; 8.Univ Pittsburgh, Sch Med, Grad Program Mol Pharmacol, Pittsburgh, PA 15261 USA; 9.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China; 10.Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA; 11.Harvard Med Sch, Boston, MA 02114 USA; 12.Chugai Pharmaceut Co Ltd, Tokyo 1038324, Japan |
推荐引用方式 GB/T 7714 | Zhao, Li-Hua,Ma, Shanshan,Sutkeviciute, Ieva,et al. Structure and dynamics of the active human parathyroid hormone receptor-1[J]. SCIENCE,2019,364(6436):148-+. |
APA | Zhao, Li-Hua.,Ma, Shanshan.,Sutkeviciute, Ieva.,Shen, Dan-Dan.,Zhou, X. Edward.,...&Zhang, Yan.(2019).Structure and dynamics of the active human parathyroid hormone receptor-1.SCIENCE,364(6436),148-+. |
MLA | Zhao, Li-Hua,et al."Structure and dynamics of the active human parathyroid hormone receptor-1".SCIENCE 364.6436(2019):148-+. |
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