7BR3

Crystal structure of the protein 1

7BR3 の概要

• エントリーDOI: 10.2210/pdb7br3/pdb
• 分子名称: Gonadotropin-releasing hormone receptor,GlgA glycogen synthase,Gonadotropin-releasing hormone receptor, (2R)-2,3-dihydroxypropyl dodecanoate, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (6 entities in total)
• 機能のキーワード: gpcr, helix, transmembrane, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62585.21

構造登録者

Cheng, L.,Shao, Z. (登録日: 2020-03-26, 公開日: 2020-10-07, 最終更新日: 2024-10-09)

主引用文献

Yan, W.,Cheng, L.,Wang, W.,Wu, C.,Yang, X.,Du, X.,Ma, L.,Qi, S.,Wei, Y.,Lu, Z.,Yang, S.,Shao, Z.
Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode.
Nat Commun, 11:5287-5287, 2020

PubMed Abstract: Gonadotrophin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone, is the main regulator of the reproductive system, acting on gonadotropic cells by binding to the GnRH1 receptor (GnRH1R). The GnRH-GnRH1R system is a promising therapeutic target for maintaining reproductive function; to date, a number of ligands targeting GnRH1R for disease treatment are available on the market. Here, we report the crystal structure of GnRH1R bound to the small-molecule drug elagolix at 2.8 Å resolution. The structure reveals an interesting N-terminus that could co-occupy the enlarged orthosteric binding site together with elagolix. The unusual ligand binding mode was further investigated by structural analyses, functional assays and molecular docking studies. On the other hand, because of the unique characteristic of lacking a cytoplasmic C-terminal helix, GnRH1R exhibits different microswitch structural features from other class A GPCRs. In summary, this study provides insight into the ligand binding mode of GnRH1R and offers an atomic framework for rational drug design.

PubMed: 33082324
DOI: 10.1038/s41467-020-19109-w

実験手法

X-RAY DIFFRACTION (2.79 Å)