PMID: 24692546

 

    Legend: Sugar

Title : Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer

Abstract :
  1. Follicle-stimulating hormone receptor ( FSHR ), a G-protein coupled receptor , is an important drug target in the development of novel therapeutics for reproductive indications
  2. 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
  3. The model predicts that FSHR binds AsnĪ±(52)-deglycosylated FSH at a 3-fold higher capacity than fully glycosylated FSH
  4. 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
  5. This study presents evidence confirming these predictions and provides crystallographic and mutagenesis data supporting the proposed model
  6. The model also provides a mechanistic explanation to the agonist and antagonist activities of thyroid-stimulating hormone receptor autoantibodies
  7. We conclude that FSHR exists as a functional trimer