8I2H

Follicle stimulating hormone receptor

8I2H の概要

• エントリーDOI: 10.2210/pdb8i2h/pdb
• EMDBエントリー: 35136
• 分子名称: Follicle-stimulating hormone receptor (1 entity in total)
• 機能のキーワード: fsh, fshr, gpcr, hormone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 76971.93

構造登録者

Duan, J.,Xu, P.,Yang, J.,Ji, Y.,Zhang, H.,Mao, C.,Luan, X.,Jiang, Y.,Zhang, Y.,Zhang, S.,Xu, H.E. (登録日: 2023-01-14, 公開日: 2023-03-22, 最終更新日: 2024-07-03)

主引用文献

Duan, J.,Xu, P.,Zhang, H.,Luan, X.,Yang, J.,He, X.,Mao, C.,Shen, D.D.,Ji, Y.,Cheng, X.,Jiang, H.,Jiang, Y.,Zhang, S.,Zhang, Y.,Xu, H.E.
Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor.
Nat Commun, 14:519-519, 2023

PubMed Abstract: Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H615 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization.

PubMed: 36720854
DOI: 10.1038/s41467-023-36170-3

実験手法

ELECTRON MICROSCOPY (6 Å)