mProX™ Human PTH2R Stable Cell Line

Li-Hua Zhao et al. "Conserved class B GPCR activation by a biased intracellular agonist." Nature, 2023
The authors of this study developed a high-resolution structure of the human parathyroid hormone 1 receptor (PTH1R) in complex with the stimulatory G protein (G(s)) and a small-molecule agonist, PCO371. This revealed an unexpected binding mode of PCO371 at the cytoplasmic interface of PTH1R with G(s). The binding site for PCO371 is different from all previously reported sites for small molecules or peptide ligands in class B G-protein-coupled receptors (GPCRs). The researchers also found that a single alteration in PTH2R and two residue alterations in glucagon-like peptide 1 receptor (GLP1R) allow these receptors to respond to PCO371. Functional assays showed that PCO371 is a G-protein-biased agonist that does not promote PTH1R-mediated arrestin signalling. These results provide new insights for designing small-molecule agonists for PTH1R and other class B GPCRs. They also define a specific receptor conformation that is only activated by G-proteins and not arrestin, which can aid in the development of different types of class B GPCR small-molecule agonists for various therapeutic purposes.
Li-Hua Zhao et al. "Conserved class B GPCR activation by a biased intracellular agonist." Nature, 2023
Pubmed: 37524305   DOI: 10.1038/s41586-023-06467-w

Cristina Dettori et al. "Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System." Journal of personalized medicine, 24 Apr. 2023
The role of Parathyroid Hormone (PTH) in maintaining calcium homeostasis has been well established, with direct effects on bone and kidneys and indirect effects on the intestine. However, there is a wider range of PTH-related peptides that have been found to have various physiological effects on different tissues and organs, including the Central Nervous System (CNS). These peptides, including PTH, PTHrP, PTHLH, and TIP39, can bind to parathyroid receptor type 1 (PTH1R) and type 2 (PTH2R), members of the type II G-protein-coupled receptor (GPCR) family. Research has shown that the PTH/PTHrP/PTH1R system is present in many areas of the brain and has been linked to protecting against neuroinflammation and neurodegeneration, as well as improving memory and reducing pain sensitivity. Similarly, the TIP39/PTH2R system has been found to play a regulatory and functional role in the brain, affecting auditory, nociceptive, and sexual maturation functions. This review aims to provide an overview of the distribution and functions of PTH-related peptides in the CNS and to highlight areas that require further research.
Cristina Dettori et al. "Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System." Journal of personalized medicine, 24 Apr. 2023
Pubmed: 37240884   DOI: 10.3390/jpm13050714