Year of Publication


Document Type



Arts and Sciences



First Advisor

Robert Guthrie


Precise control of physiological phenomena is performed by various kinds of receptormediated signaling. The vast majority of receptors belong to the superfamily of G proteincoupled receptors (GPCRs), which form one of the largest protein families. In theclassical model of GPCR signaling, stimulation of seven transmembrane spanning GPCRleads to the activation of heterotrimeric G proteins, which dissociate into a and bgsubunits. The subunits activate effector molecules, which include second messengergenerating systems, giving rise to various kinds of cellular responses. The LH/CGreceptor is a member of the glycoprotein hormone receptor family along with the FSHand TSH receptors, which belongs to the GPCR superfamily. Human chorionicgonadotropin (hCG) binds to the exodomain of LH/CG receptor and the resulting hCGexodomaincomplex is thought to interact with the endodomain of the receptor to bringabout hormone signal.Unfortunately, little evidence is available for the precise hormonecontact points in the exo domain and endo domain of the receptor. The affinity ofhormone binding to the exodomain was enhanced when the endodomain was truncated.This suggests that the endodomain modulates the hormone binding to the exodomain ofthe receptor. To understand this, the role of exoloop 2 on the modulation of high affinityhormone binding to the exodomain was studied using photoaffinity labeling technique.