Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor.

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 H615^7.42 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonist

SUBMITTER: Duan J 

PROVIDER: S-EPMC9889800 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature