4MQW : Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)

  • Xuliang Jiang (Contributor)
  • Xiaoyan Chen (Contributor)
  • Heli Liu (Contributor)
  • Xiaolin He (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2014-04-09
Deposition Date:2013-09-16
Revision Date:2014-06-18#2014-09-24
Molecular Weight:199817.16
Macromolecule Type:Protein
Residue Count:1722
Atom Site Count:11643

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.
Date made available2014

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