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）参与广泛的生理过程，将不同类型的细胞外刺激转化为细胞内信号。它们代表了当今最重要的治疗目标之一。尽管它们至关重要，但对于信号转导，桥接细胞外配体结合与细胞内G蛋白激活的分子机制知之甚少。该研究旨在利用表面增强红外吸收光谱（SEIRA）在纳米结构金表面上探索gpcr中配体与蛋白质的相互作用。这种新的光谱方法将结合膜蛋白在seira活性表面的功能吸附，从视紫红质作为模型系统开始，扩展到β-肾上腺素能、胰高血糖素和趋化因子受体，用于不同gpcr的研究。该技术允许在类似天然环境的分子水平上探测配体诱导的受体结构变化，并研究GPCR激活的不同方面及其与周围脂质基质的相互作用。更深入地了解蛋白质-配体相互作用和受体激活的分子细节不仅是基础科学兴趣，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.