The role of lipid composition for insertion and stabilization of amino acids in membranes
The role of lipid composition for insertion and stabilization of amino acids in membranes
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DOI：
10.1063/1.3129863
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发表时间：
2009-05-14
影响因子：
4.4
通讯作者：
Lindahl, Erik
中科院分区：
文献类型：
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作者：
Johansson, Anna C. V.;Lindahl, Erik
虽然大多数膜蛋白螺旋明显是疏水性的，但最近的实验表明，可以将略微疏水的螺旋插入双层中，并且表明带电残基的体内插入自由能较低，例如精氨酸为几千卡。相比之下，许多生物物理模拟研究预测双层内部接近纯疏水环境，对亲水氨基酸有很大的惩罚，但实验规模在从序列预测实际膜蛋白方面明显更好。在这里，我们系统地研究了自由能谱对脂质特性的依赖性，包括尾长、饱和度、头基氢键强度和电荷，目的都是为了看看体内插入是否可以全部或部分地由内质网（ER）膜的脂质组成来解释，以及溶剂化特性是否可以帮助解释蛋白质功能如何依赖于脂质。我们发现脂质电荷对于稳定双层内的带电氨基酸很重要（例如，对于离子通道），较厚的双层对亲水侧链的溶剂化成本较高，并且头基氢键强度决定了脂质作为疏水/亲水溶剂的适应性。不同的自由能分布都没有接近低表观体内插入成本，这表明无论特定的内质网膜成分如何，当前的实验结果都不能用正常的脂质类型变化来解释。
While most membrane protein helices are clearly hydrophobic, recent experiments have indicated that it is possible to insert marginally hydrophobic helices into bilayers and have suggested apparent in vivo free energies of insertion for charged residues that are low, e.g., a few kcals for arginine. In contrast, a number of biophysical simulation studies have predicted that the bilayer interior is close to a pure hydrophobic environment with large penalties for hydrophilic amino acids-and yet the experimental scales do significantly better at predicting actual membrane proteins from sequence. Here, we have systematically studied the dependence of the free energy profiles on lipid properties, including tail length, saturation, headgroup hydrogen bond strength, and charge, both to see to whether the in vivo insertion can be explained in whole or part from lipid composition of the endoplasmic reticulum (ER) membranes, and if the solvation properties can help interpret how protein function depends on the lipids. We find that lipid charge is important to stabilize charged amino acids inside the bilayer (with implications, e.g., for ion channels), that thicker bilayers have higher solvation costs for hydrophilic side chains, and that headgroup hydrogen bond strength determines how adaptive the lipids are as a hydrophobic/hydrophilic solvent. None of the different free energy profiles are even close to the low apparent in vivo insertion cost, which suggests that regardless of the specific ER membrane composition the current experimental results cannot be explained by normal lipid-type variation.