| Literature DB >> 30975883 |
Li-Hua Zhao1, Shanshan Ma1,2, Ieva Sutkeviciute3, Dan-Dan Shen4, X Edward Zhou5, Parker W de Waal5, Chen-Yao Li1,2, Yanyong Kang1, Lisa J Clark3,6, Frederic G Jean-Alphonse3, Alex D White3,7, Dehua Yang1, Antao Dai1, Xiaoqing Cai1, Jian Chen8, Cong Li8, Yi Jiang1, Tomoyuki Watanabe9, Thomas J Gardella9, Karsten Melcher5, Ming-Wei Wang10,8, Jean-Pierre Vilardaga11, H Eric Xu10,5, Yan Zhang12.
Abstract
The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation.Entities:
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Year: 2019 PMID： 30975883 PMCID： PMC6929210 DOI： 10.1126/science.aav7942
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728