The parathyroid hormone (PTH) type 1 receptor (PTHR) is the canonical G protein-coupled receptor (GPCR) for PTH and PTH-related protein (PTHrP) and the key regulator of calcium homeostasis and bone turnover. PTHR function is critical for human health to maintain homeostatic control of ionized serum Ca2+ levels and has several unusual signaling features, such as endosomal cAMP signaling, that are well-studied but not structurally understood. In this review, we discuss how recently solved high resolution near-atomic structures of hormone-bound PTHR in its inactive and active signaling states and discovery of extracellular Ca2+ allosterism shed light on the structural basis for PTHR signaling and function.

中文翻译：

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PTH/PTHrP 受体信号、变构和结构

甲状旁腺激素 (PTH) 1 型受体 (PTHR) 是 PTH 和 PTH 相关蛋白 (PTHrP) 的经典 G 蛋白偶联受体 (GPCR)，是钙稳态和骨转换的关键调节剂。PTHR 功能对于维持离子化血清 Ca2+ 水平的稳态控制对于人类健康至关重要，并且具有几个不同寻常的信号传导特征，例如内体 cAMP 信号传导，这些特征已得到充分研究，但在结构上尚不清楚。在这篇综述中，我们讨论了最近如何解决处于非活动和活动信号状态的激素结合 PTHR 的高分辨率近原子结构，以及细胞外 Ca2+ 变构现象的发现阐明了 PTHR 信号和功能的结构基础。