8HA0

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

8HA0 の概要

• エントリーDOI: 10.2210/pdb8ha0/pdb
• EMDBエントリー: 34585 34587 34598
• 分子名称: Guanine nucleotide-binding protein g(s) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total)
• 機能のキーワード: pth1r, gpcr, lipid binding protein-hormone-immune system complex, lipid binding protein/hormone/immune system
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 169738.78

構造登録者

Zhao, L.,Xu, H.E.,Yuan, Q. (登録日: 2022-10-26, 公開日: 2022-12-21, 最終更新日: 2024-10-16)

主引用文献

Zhao, L.H.,Yuan, Q.N.,Dai, A.T.,He, X.H.,Chen, C.W.,Zhang, C.,Xu, Y.W.,Zhou, Y.,Wang, M.W.,Yang, D.H.,Xu, H.E.
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.
Acta Pharmacol.Sin., 44:1227-1237, 2023

PubMed 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.

PubMed: 36482086
DOI: 10.1038/s41401-022-01032-z

実験手法

ELECTRON MICROSCOPY (2.62 Å)