6NBF

Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein

6NBF の概要

• エントリーDOI: 10.2210/pdb6nbf/pdb
• EMDBエントリー: 0410
• 分子名称: Parathyroid hormone/parathyroid hormone-related peptide receptor, Long-acting parathyroid hormone analog, Gs protein alpha subunit, ... (8 entities in total)
• 機能のキーワード: parathyroid hormone receptor, gpcr, class b gpcr, gpcr-g protein complex, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 165730.34

構造登録者

Zhao, L.-H.,Ma, S.,Sutkeviciute, I.,Shen, D.-D.,Zhou, X.E.,de Waal, P.P.,Li, C.-Y.,Kang, Y.,Clark, L.J.,Jean-Alphonse, F.G.,White, A.D.,Xiao, K.,Yang, D.,Jiang, Y.,Watanabe, T.,Gardella, T.J.,Melcher, K.,Wang, M.-W.,Vilardaga, J.-P.,Xu, H.E.,Zhang, Y. (登録日: 2018-12-07, 公開日: 2019-04-17, 最終更新日: 2024-10-30)

主引用文献

Zhao, L.H.,Ma, S.,Sutkeviciute, I.,Shen, D.D.,Zhou, X.E.,de Waal, P.W.,Li, C.Y.,Kang, Y.,Clark, L.J.,Jean-Alphonse, F.G.,White, A.D.,Yang, D.,Dai, A.,Cai, X.,Chen, J.,Li, C.,Jiang, Y.,Watanabe, T.,Gardella, T.J.,Melcher, K.,Wang, M.W.,Vilardaga, J.P.,Xu, H.E.,Zhang, Y.
Structure and dynamics of the active human parathyroid hormone receptor-1.
Science, 364:148-153, 2019

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 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.

PubMed: 30975883
DOI: 10.1126/science.aav7942

実験手法

ELECTRON MICROSCOPY (3 Å)