Ion channels and G protein-coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP2 plays a key role in regulating Kv and Kir channels. Likewise, several recent cryo-EM structures of TRP channels have revealed bound lipids, including PIP2 and cholesterol. Among the pentameric ligand-gated ion channel family, structural and biophysical studies suggest the M4 TM helix may act as a lipid sensor, e.g., forming part of the binding sites for neurosteroids on the GABAA receptor. Structures of GPCRs have revealed multiple cholesterol sites, which may modulate both receptor dynamics and receptor oligomerization. PIP2 also interacts with GPCRs and may modulate their interactions with G proteins. Overall, it is evident that multiple lipid binding sites exist on channels and receptors that modulate their function allosterically and are potential druggable sites.

中文翻译：

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离子通道和 G 蛋白偶联受体的脂质依赖性调节：来自结构和模拟的见解。

离子通道和 G 蛋白偶联受体 (GPCRs) 受其膜环境中的脂质调节。结构研究与生物物理和分子模拟研究相结合，揭示了特定脂质在膜蛋白结构上的相互作用位点。对于 K 通道，PIP2 在调节 Kv 和 Kir 通道中起关键作用。同样，最近 TRP 通道的几个低温 EM 结构揭示了结合的脂质，包括 PIP2 和胆固醇。在五聚体配体门控离子通道家族中，结构和生物物理研究表明 M4 TM 螺旋可以作为脂质传感器，例如，形成 GABAA 受体上神经甾体结合位点的一部分。GPCRs 的结构揭示了多个胆固醇位点，这些位点可以调节受体动力学和受体寡聚化。PIP2 还与 GPCR 相互作用，并可能调节它们与 G 蛋白的相互作用。总体而言，很明显，通道和受体上存在多个脂质结合位点，这些位点通过变构调节其功能并且是潜在的可药用位点。