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Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1

文献类型：期刊论文

作者Zhao, Li-hua2,3; Yuan, Qing-ning2; Dai, An-tao2,4; He, Xin-heng2,3; Chen, Chuan-wei1; Zhang, Chao5; Xu, You-wei2; Zhou, Yan2,4; Wang, Ming-wei1,6,7; Yang, De-hua2,3,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2022-12-08
页码11
关键词G protein- coupled receptors parathyroid hormone PTH-related peptide PTH receptor-1 cryo-electron microscopy structure osteoporosis
ISSN号1671-4083
DOI10.1038/s41401-022-01032-z
通讯作者Zhao, Li-hua(zhaolihuawendy@simm.ac.cn) ; Yang, De-hua(dhyang@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 angstrom and 3.25 angstrom, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders.
WOS关键词ABALOPARATIDE ; PEPTIDE ; CONFORMATIONS ; SELECTIVITY ; DYNAMICS ; INSIGHTS ; PTHRP
资助项目National Natural Science Foundation of China[32071203] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81973373] ; National Key R&D Program of China[2019YFA0904200] ; Young Innovator Association of CAS[2018325] ; SA-SIBS Scholarship Program ; Ministry of Science and Technology (China)[2018YFA0507002] ; Ministry of Science and Technology (China)[2018YFA0507000] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project[18ZR1447800] ; Shanghai Municipal Science and Technology Major Project[21JC1401600] ; CAS Strategic Priority Research Program[XDB08020303]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000895548500002
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/304267]  
专题中国科学院上海药物研究所
通讯作者Zhao, Li-hua; Yang, De-hua; Xu, H. Eric
作者单位1.Res Ctr Deepsea Bioresources, Sanya 572025, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct & Funct Drug Targets, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
5.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
6.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
7.Univ Tokyo, Sch Sci, Dept Chem, Tokyo 1130033, Japan
推荐引用方式
GB/T 7714		 Zhao, Li-hua,Yuan, Qing-ning,Dai, An-tao,et al. Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1[J]. ACTA PHARMACOLOGICA SINICA,2022:11.
APA Zhao, Li-hua.,Yuan, Qing-ning.,Dai, An-tao.,He, Xin-heng.,Chen, Chuan-wei.,...&Xu, H. Eric.(2022).Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.ACTA PHARMACOLOGICA SINICA,11.
MLA Zhao, Li-hua,et al."Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1".ACTA PHARMACOLOGICA SINICA (2022):11.

入库方式： OAI收割

来源：上海药物研究所

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