In recent decades intensive studies on the glycoprotein-hormone receptors (GPHRs) and their respective hormones have provided a number of molecular insights into the relationship between the structure and function of these proteins. This knowledge includes an understanding of hormone binding, of naturally occurring mutations nad mechanisms of signal transduction and G-protein binding processes.
Together with the relaxin family peptide receptors (RxFP) the GPHRs belong to the Leucine-rich repeat containing receptors (LGRs), a subgroup of class A G-protein coupled receptors (GPCR). The orphan Leucine-rich repeat containing receptors 46 (LGRs 46) are partially more homologous to the GPHRs by amino acid sequences than the RxFP receptors 12 (formerly LGR 7 and 8, respectively). In contrast to a growing number of data for the RXFP receptors, the functional and physiological role of the orphan LGRs 46 has not yet been determined. We analysed and provide here sequence-structure similarities between the homologous GPHRs and LGR4 regarding potential ligand binding sites and structural determinants of intramolecular signal transduction.
Additionally, interesting new findings concerning the ancient glycoprotein-hormone (GPH) thyrostimulin have been published previously. Thyrostimulin is an agonist for the TSHR. Utilizing the knowledge about structurefunction relationships in GPHRs and their hormones, we initially built homology models of thyrostimulin. In comparison to GPH/GPHR complexes these models not only help to describe properties of thyrostimulin more precisely, but also to draw conclusions regarding potential modes of hormone binding.
In summary, here we attempt to extract new molecular information concerning proteins with unknown but potentially important function in physiological processes by comparative analyses between homologous family members.
25 - 29 Apr 2009
European Society of Endocrinology