中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Structure and dynamics of the active human parathyroid hormone receptor-1

文献类型：期刊论文

作者Zhao, Li-Hua5; Ma, Shanshan5,6; Sutkeviciute, Ieva7; Shen, Dan-Dan8,9; Zhou, X. Edward10; de Waal, Parker W.10; Li, Chen-Yao5,6; Kang, Yanyong5; Clark, Lisa J.7,11; Jean-Alphonse, Frederic G.7
刊名SCIENCE
出版日期2019-04-12
卷号364期号:6436页码:148-+
ISSN号0036-8075
DOI10.1126/science.aav7942
通讯作者Wang, Ming-Wei(mwwang@simm.ac.cn) ; Vilardaga, Jean-Pierre(jpv@pitt.edu) ; Xu, H. Eric(eric.xu@vai.org) ; Zhang, Yan(zhang_yan@zju.edu.cn)
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.
WOS关键词CRYO-EM STRUCTURE ; GLP-1 RECEPTOR ; PTHRP RECEPTOR ; BINDING ; ACTIVATION ; RECOGNITION ; VALIDATION ; MECHANISM ; RESPONSES ; DOMAINS
资助项目National Key Basic Research Program of China[2018YFC1003600] ; Zhejiang Province Science Fund for Distinguished Young Scholars[LR19H310001] ; Shanghai Science and Technology Development Fund[18ZR1447800] ; Shanghai Science and Technology Development Fund[16ZR1407100] ; Young Innovator Association of CAS[2018325] ; SA-SIBS Scholarship Program ; Fudan-SIMM Joint Research Fund[FU-SIMM-20174003] ; National Key R&D Program of China[2018YFA0507000] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-002-005] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09735-001] ; National Natural Science Foundation of China[31300245] ; National Natural Science Foundation of China[81573479] ; National Natural Science Foundation of China[81773792] ; Ministry of Science and Technology (China)[2012ZX09301001] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[2013CB910600] ; Ministry of Science and Technology (China)[XDB08020303] ; Ministry of Science and Technology (China)[2013ZX09507001] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1-CC] ; Jay and Betty Van Andel Foundation ; National Institutes of Health[GM127710] ; National Institutes of Health[R01-DK102495] ; National Institutes of Health[R01-DK111427] ; National Institutes of Health[R01-DK116780] ; National Institutes of Health[DK11794] ; National Institutes of Health[T32-GM008424] ; Cotswold Foundation Fellowship Awards
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000464620000035
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/290116]  
专题中国科学院上海药物研究所
通讯作者Wang, Ming-Wei; Vilardaga, Jean-Pierre; Xu, H. Eric; Zhang, Yan
作者单位1.Chugai Pharmaceut Co Ltd, Tokyo 1038324, Japan
2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
3.Harvard Med Sch, Boston, MA 02114 USA
4.Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA
8.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China
9.Zhejiang Univ, Sch Med, Dept Biophys, Hangzhou 310058, Zhejiang, Peoples R China
10.Van Andel Res Inst, Innovat & Integrat Program, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA
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-+.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。