Human Follicle-Stimulating Hormone Complexed with its Receptor

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Crystal Structure of Human Follicle-Stimulating Hormone Complexed with its Receptor

Publication Abstract from PubMed

Follicle-stimulating hormone (FSH) is central to reproduction in mammals. It acts through a G-protein-coupled receptor on the surface of target cells to stimulate testicular and ovarian functions. We present here the 2.9-A-resolution structure of a partially deglycosylated complex of human FSH bound to the extracellular hormone-binding domain of its receptor (FSHR(HB)). The hormone is bound in a hand-clasp fashion to an elongated, curved receptor. The buried interface of the complex is large (2,600 A2) and has a high charge density. Our analysis suggests that all glycoprotein hormones bind to their receptors in this mode and that binding specificity is mediated by key interaction sites involving both the common alpha- and hormone-specific beta-subunits. On binding, FSH undergoes a concerted conformational change that affects protruding loops implicated in receptor activation. The FSH-FSHR(HB) complexes form dimers in the crystal and at high concentrations in solution. Such dimers may participate in transmembrane signal transduction.

Structure of human follicle-stimulating hormone in complex with its receptor., Fan QR, Hendrickson WA, Nature. 2005 Jan 20;433(7023):269-77. PMID:15662415

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

Known disease associated with this structure: Follicle-stimulating hormone deficiency, isolated OMIM:[136530], Ovarian dysgenesis 1 OMIM:[136435], Ovarian hyperstimulation syndrome OMIM:[136435], Ovarian response to FSH stimulation OMIM:[136435], Ovarian sex cord tumors OMIM:[136435]

About this Structure

 

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FSH binding to the leucine-rich domain of Follicle Stimulating Hormone Receptor (1fl7 morphing to 1xwd, resolution 2.92Å)


1XWD is a 6 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.


The leucine-rich domain of the receptor ; leucine-rich repeats often are horseshoe- or arc-shaped.

Reference

  • Fan QR, Hendrickson WA. Structure of human follicle-stimulating hormone in complex with its receptor. Nature. 2005 Jan 20;433(7023):269-77. PMID:15662415 doi:10.1038/nature03206

See also

Page originally seeded at 1xwd by OCA on Tue Feb 17 21:34:49 2009

Proteopedia Page Contributors and Editors (what is this?)

Wayne Decatur, Michal Harel, Alexander Berchansky

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