4MQW: Structure Of Follicle-stimulating Hormone In Complex With The Entire Ectodomain Of Its Receptor (p31)

Citation:
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 Asnalpha(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.
PDB ID: 4MQWDownload
MMDB ID: 119037
PDB Deposition Date: 2013/9/16
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4MQW: trimeric; determined by author and by software (PISA)
Molecular Components in 4MQW
Label Count Molecule
Proteins (3 molecules)
1
Glycoprotein Hormones, Alpha Polypeptide
Molecule annotation
1
Follitropin Subunit Beta(Gene symbol: FSHB)
Molecule annotation
1
Follicle-stimulating Hormone Receptor(Gene symbol: FSHR)
Molecule annotation
Chemicals (10 molecules)
1
6
2
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.