Advances in the molecular understanding of gonadotropins-receptors interactions

Abstract

The extracellular domain (ECD) of gonadotropin receptors belong to the leucine-rich repeat (LRR) protein superfamily and their transmembrane domain (TMD) is characteristic of the seven α-helices G-protein-coupled receptors (GPCR). The availability of the X-ray strutures of porcine ribonuclease inhibitor (RI), a LRR protein, and bacteriorhodopsin (bR) allows the construction of 3D models of the ECD and the TMD of gonadotropin receptors, respectively. The predicted models are to a large extent consistent with currently available biochemical and mutational data. The models provide a reliable basis for understanding how the hormone binds and activates its receptor. The ECD, in particular the LRR region, serves as a baseball glove which efficiently catches the large hormone and optimally orient the appropriate parts of it for interaction with the seven-transmembrane-helix domain of the receptor. This in turn is expected to lead to a conformational change to be sensed by the appropriate G-protein complex leading to the stimulation of cAMP synthesis and steroids production.