PTH1R / GPCR / LIPID BINDING PROTEIN-HORMONE-IMMUNE SYSTEM complex
機能・相同性
機能・相同性情報
parathyroid hormone receptor binding / type 1 parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / positive regulation of osteoclast proliferation / negative regulation of apoptotic process in bone marrow cell / response to parathyroid hormone / positive regulation of cell proliferation in bone marrow / macromolecule biosynthetic process / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway ...parathyroid hormone receptor binding / type 1 parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / positive regulation of osteoclast proliferation / negative regulation of apoptotic process in bone marrow cell / response to parathyroid hormone / positive regulation of cell proliferation in bone marrow / macromolecule biosynthetic process / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway / magnesium ion homeostasis / positive regulation of signal transduction / response to fibroblast growth factor / phosphate ion homeostasis / cAMP metabolic process / response to vitamin D / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Class B/2 (Secretin family receptors) / G protein-coupled peptide receptor activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / negative regulation of chondrocyte differentiation / osteoblast development / G alpha (i) signalling events / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / photoreceptor outer segment membrane / G alpha (q) signalling events / peptide hormone receptor binding / positive regulation of inositol phosphate biosynthetic process / G alpha (i) signalling events / spectrin binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / bone mineralization / alkylglycerophosphoethanolamine phosphodiesterase activity / peptide hormone binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / photoreceptor outer segment / Rho protein signal transduction / chondrocyte differentiation / positive regulation of glycogen biosynthetic process / bone resorption / positive regulation of bone mineralization / response to cadmium ion / cell maturation / homeostasis of number of cells within a tissue / photoreceptor inner segment / cardiac muscle cell apoptotic process / skeletal system development / positive regulation of D-glucose import / response to lead ion / hormone activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / intracellular calcium ion homeostasis / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of taste / cell-cell signaling / signaling receptor complex adaptor activity 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
32071203
中国
引用
ジャーナル: Acta Pharmacol Sin / 年: 2023 タイトル: Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1. 著者: Li-Hua Zhao / Qing-Ning Yuan / An-Tao Dai / Xin-Heng He / Chuan-Wei Chen / Chao Zhang / You-Wei Xu / Yan Zhou / Ming-Wei Wang / De-Hua Yang / H Eric Xu / 要旨: 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 ...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.