Structural and functional characterization of G protein-coupled adenosine receptors and the orphan receptor GPR143

Abstract

The present thesis deals with the characterization of G protein-coupled receptors (GPCRs) and their interaction with modulators on a molecular level. We focused on the structural and functional investigation of different types of GPCRs: the well known, previously crystallized adenosine A2A receptor and its closely related, but much less investigated relative, the adenosine A2B receptor, both of which are promising drug targets, and the underexplored orphan receptor GPR143, an intracellular GPCR which is involved in Ocular Albinism type I. Our goal was to study the impact of structural changes of GPCRs on ligand binding, signaling, and ligand selectivity as well as their allosteric modulation by interaction with other proteins. The results of our studies do not only expand the knowledge of basic biological processes, but they will also contribute to design of potent and selective receptor ligands which have potential as novel therapeutics.