Open AccessMolecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2
Author(s) -
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. Y. Xu,
Dehua Yang,
Mingwei Wang
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2101279118
Subject(s) - g protein coupled receptor , heterotrimeric g protein , receptor , mutagenesis , ligand (biochemistry) , transmembrane domain , parathyroid hormone , biology , microbiology and biotechnology , chemistry , g protein , mutation , biochemistry , medicine , calcium , gene
Significance The high-resolution cryogenic electron microscopy structure of the human parathyroid hormone receptor 2 (PTH2R), in complex with an endogenous tuberoinfundibular peptide (TIP39) and a heterotrimeric Gs protein, reveals that the unique loop conformation at the N terminus of TIP39 is indispensable for PTH2R activation, as the deletion of which results in a potent PTH2R antagonist TIP(7-39). The naturally occurring mutation G258D impairs the receptor signaling such as cAMP accumulation. This finding provides a potential molecular mechanism for syndromic short stature.