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-Structure paper
Title | Structure and dynamics of the active human parathyroid hormone receptor-1. |
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Journal, issue, pages | Science, Vol. 364, Issue 6436, Page 148-153, Year 2019 |
Publish date | Apr 12, 2019 |
Authors | Li-Hua Zhao / Shanshan Ma / Ieva Sutkeviciute / Dan-Dan Shen / X Edward Zhou / Parker W de Waal / Chen-Yao Li / Yanyong Kang / Lisa J Clark / Frederic G Jean-Alphonse / Alex D White / Dehua Yang / Antao Dai / Xiaoqing Cai / Jian Chen / Cong Li / Yi Jiang / Tomoyuki Watanabe / Thomas J Gardella / Karsten Melcher / Ming-Wei Wang / Jean-Pierre Vilardaga / H Eric Xu / Yan Zhang / |
PubMed 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 ...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. |
External links | Science / PubMed:30975883 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 4.0 Å |
Structure data | EMDB-0410, PDB-6nbf: |
Chemicals | ChemComp-CLR: ChemComp-PLM: |
Source |
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Keywords | SIGNALING PROTEIN / Parathyroid hormone receptor / GPCR / Class B GPCR / GPCR-G protein complex |