1XWD

Crystal Structure of Human Follicle Stimulating Hormone Complexed with its Receptor

Summary for 1XWD

• Entry DOI: 10.2210/pdb1xwd/pdb
• Descriptor: Glycoprotein hormones alpha chain, Follitropin beta chain, Follicle stimulating hormone receptor, ... (8 entities in total)
• Functional Keywords: hormone-receptor complex, leucine-rich repeats, cysteine-knot motif, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 105333.99

Authors

Fan, Q.R.,Hendrickson, W.A. (deposition date: 2004-10-30, release date: 2005-01-25, Last modification date: 2023-08-23)

Primary citation

Fan, Q.R.,Hendrickson, W.A.
Structure of human follicle-stimulating hormone in complex with its receptor.
Nature, 433:269-277, 2005

PubMed Abstract: 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.

PubMed: 15662415
DOI: 10.1038/nature03206

Experimental method

X-RAY DIFFRACTION (2.92 Å)