In Vitro Expressed GPGR Inserted in Polymersome Membranes for Ligand-Binding Studies

摘要

G-protein-coupled receptors (GPCRs) constitute the largest gene family in the human genome (ca. 2 % of all genes) and play an indispensable role in cell communication, cell adhesion, and signal transduction. Given their central role in diverse physiological processes, it comes as no surprise that these seven-transmembrane domain proteins are significantly involved in many diseases and, indeed, about 40% of all marketed drugs or those in development target GPCRs. For the majority of these receptors, however, the structure-function relationships remain elusive. Furthermore, there is a considerable number of orphan receptors with unknown endogenous ligands. As such, substantial effort is directed towards the development of ligand-binding assays to identify either endogenous ligands or to screen for new drug leads. A key determinant for the successful development of screening assays is the stable immobilization of GPCRs in an active conformation, preferably onto surfaces, to allow for a reliable micro-array-based screening format. Upon a screening hit such ligands can then be further tested in functional assays.