Lipids Alter Rhodopsin Function via Ligand-like and Solvent-like Interactions.
Lipids Alter Rhodopsin Function via Ligand-like and Solvent-like Interactions.
复制标题
脂质通过类配体和类溶剂相互作用改变视紫红质功能。
DOI：
10.1016/j.bpj.2017.11.021
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发表时间：
2018
影响因子：
3.4
通讯作者：
Grossfield,Alan
中科院分区：
文献类型：
--
作者：
Salas-Estrada,LeslieA;Leioatts,Nicholas;Romo,TodD;Grossfield,Alan
视紫红质是一种典型的G蛋白偶联受体，是一种能够感知微弱光的膜蛋白。已知这种高效的光感受器对其微环境的组成敏感，但这种受体功能和结构稳定性的微调调节的分子机制尚未完全理解。有两种相互竞争的假设来解释这是如何发生的：1）脂质调节通过溶剂样相互作用发生，其中脂质组成控制膜特性，如疏水厚度，这反过来又调节蛋白质的构象平衡;或2）蛋白质-脂质相互作用是配体样的，具有特定的热点和长寿命的结合事件。通过分析五种不同状态的视紫红质的全原子分子动力学模拟的合奏，我们表明，在受体激活后，在膜中发生的局部有序效应。同样，二十二碳六烯酸酰基尾部和磷脂酰乙醇胺头基的行为就像弱配体，优先以非活性样构象与受体结合，并诱导微妙但显着的结构变化。
Rhodopsin, a prototypical G protein-coupled receptor, is a membrane protein that can sense dim light. This highly effective photoreceptor is known to be sensitive to the composition of its lipidic environment, but the molecular mechanisms underlying this fine-tuned modulation of the receptor's function and structural stability are not fully understood. There are two competing hypotheses to explain how this occurs: 1) lipid modulation occurs via solvent-like interactions, where lipid composition controls membrane properties like hydrophobic thickness, which in turn modulate the protein's conformational equilibrium; or 2) protein-lipid interactions are ligand-like, with specific hot spots and long-lived binding events. By analyzing an ensemble of all-atom molecular dynamics simulations of five different states of rhodopsin, we show that a local ordering effect takes place in the membrane upon receptor activation. Likewise, docosahexaenoic acid acyl tails and phosphatidylethanolamine headgroups behave like weak ligands, preferentially binding to the receptor in inactive-like conformations and inducing subtle but significant structural changes.