Exploring ligand-protein interaction in G protein-coupled receptors using surface-enhanced infrared absorption spectroscopy of membrane protein monolayers on nano-structured gold surfaces

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G protein-coupled receptors (GPCRs) are involved in a broad range of physiological processes transducing different types of extracellular stimuli into intracellular signals. They represent today one of the most important targets of therapeutics. Despite their crucial importance very little is known about the molecular mechanisms of signal transduction, bridging extracellular ligand binding with intracellular G protein activation. The proposed study aims at exploring ligand-protein interactions in GPCRs using surface-enhanced infrared absorption spectroscopy (SEIRA) on nano-structured gold surfaces. This new spectroscopic method will be applied in combination with functional adsorption of membrane proteins on SEIRA-active surfaces for the study of different GPCRs, starting with rhodopsin as a model system, and extending it to β-adrenergic, glucagon and chemokine receptors. This technique allows to probe ligand-induced structural changes in the receptor on a molecular level in a native-like environment and to study different aspects of GPCR activation and their interaction with the surrounding lipid matrix. A more thorough understanding of the molecular details of protein-ligand interactions and receptor activation is not only of a fundamental scientific interest but is also highly relevant for modern drug design.