Title : Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer
Abstract :
Follicle-stimulating hormone receptor ( FSHR ), a G-protein coupled receptor , is an important drug target in the development of novel therapeutics for reproductive indications
The FSHR extracellular domains were observed in the crystal structure as a trimer , which enabled us to propose a novel model for the receptor activation mechanism
The model predicts that FSHR binds AsnĪ±(52)-deglycosylated FSH at a 3-fold higher capacity than fully glycosylated FSH
It also predicts that, upon dissociation of the FSHR trimer into monomers, the binding of glycosylated FSH , but not deglycosylated FSH , would increase 3-fold, and that the dissociated monomers would in turn enhance FSHR binding and signaling activities by 3-fold
This study presents evidence confirming these predictions and provides crystallographic and mutagenesis data supporting the proposed model
The model also provides a mechanistic explanation to the agonist and antagonist activities of thyroid-stimulating hormone receptor autoantibodies
We conclude that FSHR exists as a functional trimer