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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 

Parathyroid hormone 1 receptor: insights into structure and function.

The parathyroid hormone ( PTH) and parathyroid hormone type 1 receptor (PTH1- Rc) are major players in regulating blood calcium homeostasis. PTH1- Rc is a G protein-coupled receptor ( GPCR) and it is also activated by PTH-related protein ( PTHrP), which has potent effects in several target tissues including bone, via endocrine, paracrine, and autocrine mechanisms in prenatal and adult stages of life, and in several diseases. Another layer of complexity is added by the recently discovered PTH2- Rc subtype displaying unique tissue distribution and ligand specificity, and the potential presence in mammals of a third receptor subtype. Understanding of the mechanisms regulating PTH1- Rc gene expression, receptor desensitization, endocytosis, recycling, and intracellular signaling is advancing and provides insights to understand PTH1-Rc's role in both normal and pathophysiology. In addition, development of an experimentally based model of the PTH-PTH1- Rc complex by combining photoaffinity crosslinking, mutagenesis, conformational analysis, and molecular modeling sheds light, at the atomic resolution, on the molecular mechanisms involved in ligand binding, receptor activation, and coupling to intracellular effectors. Taken together, these lines of investigation offer not only a better understanding of GPCR mechanisms of action in general, but also contribute to the treatment of PTH/PTHrP-PTH1-Rc-related disease states and to the rational development of novel mechanism-based drugs to treat them.[1]

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