Hormone binding to the follicle-stimulating hormone receptor--crystal clear!
The receptors for the trophic hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyrotropin (TSH) play a central role in endocrinology. These receptors face the challenge to accommodate large heterodimeric glycoprotein ligands within their extracellular hormone-binding domain. Until recently, the mechanism of hormone binding and consequently the mode of receptor activation remained enigmatic. By solving the crystal structure of human follicle-stimulating hormone bound to the receptor's hormone binding domain, it has become clear that the follicle-stimulating hormone receptor grabs the glycoprotein hormone in a hand-clasp mode resulting in a hormone orientation perpendicular to the long axis of the ligand-binding domain. These findings have important ramifications for our understanding of the molecular mechanism of receptor activation and may provide a rational basis for the development of small, non-peptidic FSH receptor ligands.
Gudermann
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T
Institut für Pharmakologie und Toxikologie, Fachbereich Medizin, Philipps-Universität Marburg, Germany. guderman@staff.uni-marburg.de
Nurwakagari
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Ben-Menahem
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D
D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D019281:Dimerization; D005640:Follicle Stimulating Hormone / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D011962:Receptors, FSH / Q000737:chemistry / Q000378:metabolism*
D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone