Title : Structure of human follicle-stimulating hormone in complex with its
receptor
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