Abstract
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.
🔬 Techniques
✨ Fluorophores
🧪 Sample Preparation
🔬 Cell Lines
🏭 Microscope Brands
🧪 Reagent Suppliers
💻 Software Details
💾 Data Repositories
🏛️ Research Organizations (ROR)
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📊 Figures
Figure 1.
Modes of Parathyroid Hormone Type 1 Receptor (PTHR) Signaling.
(A) Major G protein signaling pathways triggered by PTHR activation. General principle of signaling by PTHR. Parathyroid hormone (PTH) or PTH-related protein (PTHrP) binding induces or stabilizes acti...
Figure 2.
Cryo-Electron Microscopy Structure of Active State Parathyroid Hormone Type 1 Receptor (PTHR) Bound to Long Acting Parathyroid Hormone (LA-PTH) and in Complex with Gs Heterotrimer.
(A) Overall structure of the complex in cartoon and transparent surface representation; PTHR, LA-PTH, Gu03b1s, Gu03b2, and Gu03b3 are shown in violet, orange, green, cyan, and magenta, respectively (s...
Figure 3.
Structural Dynamics of Long Acting Parathyroid Hormone (LA-PTH)u2013Parathyroid Hormone Type 1 Receptor (PTHR) Complex.
(A) Three distinct conformational states of LA-PTHu2013PTHR complex obtained from cryo-electron microscopy data analysis. PTHR and LA-PTH are shown as different shades of violet and orange, respective...
Figure 4.
Structures of Parathyroid Hormone Type 1 Receptor (PTHR) in Active (Au2013C) and Inactive (Du2013F) States.
(A) Residue interaction network within the receptor transmembrane domain (TMD) core of the active structure. Interacting residues (with interaction distances u22644 u00c5) are shown as sticks and cont...
Figure 5.
Overlay of Inactive and Active Parathyroid Hormone Type 1 Receptor (PTHR) Structures (A,B) and Structural Basis of Parathyroid Hormone (PTH)-R25 Contribution to Ca 2+ Allostery (Cu2013E).
The receptor and modified PTH (ePTH) of the inactive structure are colored dark red and pink, respectively. The receptor and long acting parathyroid hormone (LA-PTH) of the active structure are colore...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
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