ADVANCES IN THE MOLECULAR UNDERSTANDING OF GONADOTROPINS-RECEPTORS INTERACTIONS

The extracellular domain (ECD) of gonadotropin receptors belong to the leucine-rich repeal (LRR) protein superfamily and their transmembrane domain (TMD) is characteristic of the seven alpha-helices G-protein-c oupled receptors (GPCR). The availability of the X-ray structures of p orcine ribonuclease inhibitor (RI), a LRR protein, and bacteriorhodops in (bR) allows the construction of 3D models of the ECD and the TMD of gonadotropin receptors, respectively. The predicted models are to a l arge extent consistent with currently available biochemical and mutati onal data. The models provide a reliable basis for understanding how t he hormone binds and activates its receptor. The ECD, in particular th e LRR region, serves as a baseball glove which efficiently catches the large hormone and optimally orient the appropriate parts of it for in teraction with the seven-transmembrane-helix domain of the receptor. T his in turn is expected to lead to a conformational change to be sense d by the appropriate G-protein complex leading to the stimulation of c AMP synthesis and steroids production. Copyright (C) 1996 Elsevier Sci ence Ireland Ltd.