Insights into G-protein coupling preference from cryo-EM structures of G_q-bound PTH1R.

ABSTRACT: The parathyroid hormone type 1 receptor (PTH1R) is a prototypical class B1 G-protein-coupled receptor that couples to both G_q and G_s, having a crucial role in calcium homeostasis and serving as a therapeutic target for osteoporosis. Therapies targeting PTH1R face challenges because of G_q-associated prolonged signaling, which leads to bone resorption. To address this, selective activation of G_s signaling is desirable. However, the structural basis of G_q-mediated signaling remains unclear, limiting the development of signal-selective drugs. Here, we present cryo-electron microscopy structures of the PTH1R-G_q complex in two distinct extracellular conformations, demonstrating the role of N-linked glycans at N176^1.28 i

SUBMITTER: Sano FK 

PROVIDER: S-EPMC12643933 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature