@article{APS10840,
author = {Li-hua Zhao and Qing-ning Yuan and An-tao Dai and Xin-heng He and Chuan-wei Chen and Chao Zhang and You-wei Xu and Yan Zhou and Ming-wei Wang and De-hua Yang and H. Eric Xu},
title = {Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {6},
year = {2023},
keywords = {},
abstract = {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 Å and 3.25 Å, 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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10840}
}