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
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2022-12-08 |
| 页码 | 11 |
| ISSN号 | 1671-4083 |
| 关键词 | G protein- coupled receptors parathyroid hormone PTH-related peptide PTH receptor-1 cryo-electron microscopy structure osteoporosis |
| DOI | 10.1038/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 |
| 出版者 | NATURE PUBL GROUP |
| WOS记录号 | WOS:000895548500002 |
| 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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