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

G蛋白偶联受体（GPCR）参与了广泛的生理过程，将不同类型的细胞外刺激转换为细胞内信号。它们代表了当今治疗学最重要的靶标之一。尽管其至关重要的是很少有人知道的信号转导的分子机制，桥接细胞外配体结合与细胞内G蛋白激活。该研究的目的是利用纳米结构金表面的表面增强红外吸收光谱（SEIRA）探索GPCR中的配体-蛋白质相互作用。这种新的光谱方法将与膜蛋白在SEIRA活性表面上的功能性吸附相结合，用于研究不同的GPCR，从视紫红质作为模型系统开始，并将其扩展到β-肾上腺素能受体、胰高血糖素受体和趋化因子受体。这种技术允许探针配体诱导的结构变化的受体在分子水平上在一个天然的环境，并研究不同方面的GPCR激活及其与周围的脂质基质的相互作用。对蛋白质-配体相互作用和受体活化的分子细节的更透彻的理解不仅具有基本的科学兴趣，而且与现代药物设计高度相关。

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.