Xi Wang, Xi Cheng, Lihua Zhao, Yuzhe Wang, Chenyu Ye, Xinyu Zou, Antao Dai, Zhaotong Cong, Jian Chen, Qingtong Zhou, Tian Xia, Hualiang Jiang, H Eric Xu, Dehua Yang, Ming-Wei Wang
The parathyroid hormone receptor 2 (PTH2R) is a class B1 G protein-coupled receptor (GPCR) involved in the regulation of calcium transport, nociception mediation, and wound healing. Naturally occurring mutations in PTH2R were reported to cause hereditary diseases, including syndromic short stature. Here, we report the cryogenic electron microscopy structure of PTH2R bound to its endogenous ligand, tuberoinfundibular peptide (TIP39), and a heterotrimeric Gs protein at a global resolution of 2.8 Å. The structure reveals that TIP39 adopts a unique loop conformation at the N terminus and deeply inserts into the orthosteric ligand-binding pocket in the transmembrane domain...
August 10, 2021: Proceedings of the National Academy of Sciences of the United States of America