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PTH/PTHrP Receptor Signaling, Allostery, and Structures
Ieva Sutkeviciute1, Lisa J Clark2, Alex D White3
1Laboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Trends in Endocrinology and Metabolism: TEM
|November 9, 2019
Summary
Structural insights into the parathyroid hormone (PTH) type 1 receptor (PTHR) reveal its role in calcium homeostasis. Near-atomic structures illuminate PTHR signaling mechanisms and extracellular calcium allosterism.
Area of Science:
- Biochemistry
- Structural Biology
- Endocrinology
Background:
- The parathyroid hormone (PTH) type 1 receptor (PTHR) is a G protein-coupled receptor (GPCR) crucial for calcium (Ca2+) homeostasis and bone metabolism.
- Its signaling pathways, including endosomal cAMP signaling, are vital but lack structural understanding.
Purpose of the Study:
- To elucidate the structural basis of PTHR signaling and function.
- To understand the mechanisms of calcium allosterism in PTHR activation.
Main Methods:
- High-resolution near-atomic structural determination of hormone-bound PTHR.
- Analysis of inactive and active signaling states of the receptor.
Main Results:
- Recently solved structures provide near-atomic resolution of the hormone-bound PTHR.
- These structures reveal the receptor in both inactive and active signaling states.
- The discovery of extracellular Ca2+ allosterism offers new functional insights.
Conclusions:
- Near-atomic structures of PTHR provide unprecedented insights into its signaling mechanisms.
- Understanding PTHR structure is key to deciphering calcium homeostasis and bone turnover regulation.
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