Cryo-EM structures of GnRHR: Foundations for next-generation therapeutics.

ABSTRACT: Gonadotropin-releasing hormone receptor (GnRHR) is critical for reproductive health and a key therapeutic target for endocrine disorders and hormone-responsive cancers. Using high-resolution cryoelectron microscopy, we determined the structures of Sus scrofa and Xenopus laevis GnRHRs bound to mammal GnRH, uncovering conserved and species-specific mechanisms of receptor activation and G protein coupling. The conserved "U"-shaped GnRH conformation mediates high-affinity binding through key interactions with residues such as K^3.32, Y^6.51, and Y^6.52. Species-specific variations in extracellular loops and receptor-ligand contacts fine-tune receptor function, while ligand binding induces structural rearrangements, including N terminus displacement a

SUBMITTER: Shen S 

PROVIDER: S-EPMC12207466 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature