Molecular properties of the PTH/PTHrP receptor.
The receptor for parathyroid hormone (PTH) and PTH-related protein (PTHrP) is a G protein-coupled receptor (GPCR) that plays a key role in controlling blood Ca(2+) concentration and endochondral bone formation. This review focuses on the molecular mechanisms by which the receptor recognizes the PTH and PTHrP peptide ligands and transmits their signal across the cell membrane. The available data suggest that there are two principal components to the ligand-receptor interaction. First, a docking interaction between the C-terminal portion of PTH(1-34) and the N-terminal extracellular domain of the receptor; and second, a weaker interaction between the N-terminal portion of the ligand and the juxtamembrane region of the receptor, which induces signal transduction. A full understanding of these processes could lead to new PTH/PTHrP receptor ligands that are effective in controlling diseases of bone and mineral metabolism, such as osteoporosis.
Gardella
T J
TJ
Endocrine Unit and Dept of Pediatrics, Massachusetts General Hospital and Harvard Medical School, 02114, Boston, MA, USA. gardella@helix.mgh.harvard.edu
Jüppner
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1; D044183:Receptor, Parathyroid Hormone, Type 2; D018016:Receptors, Parathyroid Hormone / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
D009479:Neuropeptides; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D044183:Receptor, Parathyroid Hormone, Type 2; D018016:Receptors, Parathyroid Hormone; C400136:tuberoinfundibular peptide 39