PTH/PTHrP Receptor Signaling, Allostery, and Structures

Trends Endocrinol Metab. 2019 Nov;30(11):860-874. doi: 10.1016/j.tem.2019.07.011.


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.

Keywords: G protein-coupled receptor; allostery; cAMP; cryo-EM structure; endosomes; parathyroid hormone.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Endosomes / metabolism
  • Humans
  • Parathyroid Hormone / metabolism*
  • Receptor, Parathyroid Hormone, Type 1 / chemistry
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology


  • Parathyroid Hormone
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, G-Protein-Coupled