Jain Greeshma, Eddy Matthew T
Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
Curr Opin Struct Biol. 2025 Jun 27;94:103103. doi: 10.1016/j.sbi.2025.103103.
G protein-coupled receptors (GPCRs) function within cellular membranes, complex and dynamic environments. Rather than serving as a passive background, lipid membranes actively influence GPCR drug responses and signaling. Studies utilizing nuclear magnetic resonance (NMR) spectroscopy have revealed key insights into receptor-lipid interactions, enabled by the compatibility of NMR experiments with many different membrane systems and physiological temperature, conditions more closely reflecting the native cellular environment. NMR data have revealed new mechanistic insights that explain how specific lipids regulate GPCR activation, how bulk membrane properties influence receptor dynamics, and how different membrane mimetics affect GPCR behavior. These findings establish a framework for bridging in vitro structural studies with in vivo biological and pharmacological data.
G蛋白偶联受体（GPCRs）在细胞膜这种复杂且动态的环境中发挥作用。脂膜并非作为被动背景，而是积极影响GPCR的药物反应和信号传导。利用核磁共振（NMR）光谱学的研究揭示了受体 - 脂质相互作用的关键见解，这得益于NMR实验与许多不同膜系统以及生理温度的兼容性，这些条件更能紧密反映天然细胞环境。NMR数据揭示了新的机制见解，解释了特定脂质如何调节GPCR激活、膜整体性质如何影响受体动力学，以及不同膜模拟物如何影响GPCR行为。这些发现建立了一个将体外结构研究与体内生物学和药理学数据相联系的框架。
