Structural highlights
FunctionPublication Abstract from PubMedFollicle stimulating hormone receptor (FSHR), a G-protein coupled receptor (GPCR), is an important drug target in the development of novel therapeutics for reproductive indications. The FSHR extracellular domains are 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 N52alpha-deglycosylated FSH at a three-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 three-fold, and that the dissociated monomers would in turn enhance FSHR binding and signaling activities by three-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 (TSHR) autoantibodies. We conclude that FSHR exists as a functional trimer. Evidence for Follicle-stimulating Hormone Receptor as a Functional Trimer.,Jiang X, Fischer D, Chen X, McKenna SD, Liu H, Sriraman V, Yu HN, Goutopoulos A, Arkinstall S, He X J Biol Chem. 2014 Apr 2. PMID:24692546[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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