Inducing Conformational Changes in G Protein-Coupled Receptors by Domain Coupling

Our understanding of GPCR function has advanced considerably in the past few years primarily because advances were made in elucidating structures of several GPCRs and a new era of conformational dynamic studies of GPCRs is in fast progress. Traditional pharmacological studies in tissues and native cells yielded structure-function relationships through the manipulation of the drugs, resulting in a rich array of tools for research as well as use in therapeutics. Through the epoch of molecular cloning combined with analyses of structure-function of GPCRs, we learned the complexity of receptor subtypes, relationships within this receptor superfamily, and the broad spectrum of ligands to which GPCRs can functionally respond and regulate physiology. Modern structure and dynamic analytical approaches and ligand discoveries lead to realization of common operational principles through which GPCRs control transmembrane signal transduction and intracellular processes in mediating diverse physiological and pathophysiological pathways. This chapter focuses on one such operational principle – induction of conformational changes through domain coupling – by which GPCRs operate.