Gardella T J, Jüppner H
Endocrine Unit and Dept of Pediatrics, Massachusetts General Hospital and Harvard Medical School, 02114, Boston, MA, USA.
Trends Endocrinol Metab. 2001 Jul;12(5):210-7. doi: 10.1016/s1043-2760(01)00409-x.
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.
甲状旁腺激素（PTH）和PTH相关蛋白（PTHrP）的受体是一种G蛋白偶联受体（GPCR），在控制血钙（Ca2+）浓度和软骨内骨形成中起关键作用。本综述聚焦于该受体识别PTH和PTHrP肽配体并将其信号跨细胞膜传递的分子机制。现有数据表明，配体-受体相互作用有两个主要成分。首先，PTH（1-34）的C末端部分与受体的N末端胞外结构域之间存在对接相互作用；其次，配体的N末端部分与受体的近膜区域之间存在较弱的相互作用，可诱导信号转导。全面了解这些过程可能会产生有效的新型PTH/PTHrP受体配体，用于控制骨和矿物质代谢疾病，如骨质疏松症。
