AI Article Synopsis
- FSH is a crucial hormone for human reproduction, and its signaling via the FSH receptor can impact fertility and cause ovarian hyperstimulation syndrome.
- Cryo-EM structures of the FSH receptor show both inactive and active states, revealing how this receptor is activated by FSH and a specific compound, which helps understand its mechanisms.
- The findings also emphasize a unique residue in the FSH receptor that influences its interaction with various compounds, paving the way for new drug designs aimed at treating infertility and enhancing IVF procedures.
Article 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.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889800 | PMC |
| http://dx.doi.org/10.1038/s41467-023-36170-3 | DOI Listing |
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