Delineation of Subunit and Receptor Contact Sites by Site-Directed Mutagenesis of hCGβ

Considerable data have been amassed on the four glycoprotein hormones, chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) (1). It is well established that, within a species, the single α-subunit binds to distinct β-subunits to form bioactive holoproteins, which exhibit specificity for three G protein-coupled receptors (r) (2), LH/CGr (3), FSHr (4), and TSHr (5). Since the glycoprotein hormones contain a common α-subunit, and since both subunits are believed to participate in receptor binding (6, 7), interesting questions and models can be developed regarding subunit contact sites and hormone receptor contact sites, particularly those responsible for conferring specificity. The absence of a crystallographic structure for any member of the glycoprotein hormone family has, however, prevented a detailed understanding of these contact regions.