PTH/PTHrP Receptor Signaling, Allostery, and Structures

Publication date: November 2019Source: Trends in Endocrinology & Metabolism, Volume 30, Issue 11Author(s): Ieva Sutkeviciute, Lisa J. Clark, Alex D. White, Thomas J. Gardella, Jean-Pierre VilardagaThe 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.
Source: Trends in Endocrinology and Metabolism - Category: Endocrinology Source Type: research