The role of hydrophobic interactions in positioning of peripheral proteins in membranes.
The role of hydrophobic interactions in positioning of peripheral proteins in membranes.
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DOI：
10.1186/1472-6807-7-44
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发表时间：
2007-06-29
影响因子：
--
通讯作者：
Mosberg HI
中科院分区：
文献类型：
--
作者：
Lomize AL;Pogozheva ID;Lomize MA;Mosberg HI
已经确定了许多外周膜蛋白的三维（3D）结构。这些蛋白质的生物活性、稳定性和构象取决于它们相对于脂质双层的空间位置。然而，这些位置通常是不确定的。我们报告的第一个大规模的计算研究单调/外周蛋白质与已知的三维结构。476个蛋白质的最佳平移和旋转位置的确定通过最小化能量的蛋白质从水转移到脂质双层，这是近似的烃板与癸二烯样的极性和界面区域，其特征在于由水渗透配置文件。预测的膜结合位点，蛋白质倾斜角和膜穿透深度与自旋标记，化学修饰，荧光，NMR，诱变，和其他实验研究的53个外周蛋白质和肽是一致的。实验的外周蛋白的膜结合亲和力的情况下，不涉及螺旋线圈过渡，脂质的特异性结合，或主要是静电协会再现。所有检测的外周蛋白和肽与计算的疏水膜边界、亚细胞定位、拓扑结构、结构分类和实验参考的坐标可通过膜中蛋白质取向（OPM）数据库获得。不同的外周蛋白质和肽在脂质双层中的位置可以使用它们的3D结构准确地预测，所述3D结构代表适当的膜结合构象和低聚状态，并且具有存在的膜结合元件。隐式溶剂化模型的成功表明，疏水相互作用通常足以确定蛋白质在膜中的空间位置，即使当静电相互作用或脂质的特异性结合是实质性的。我们的研究结果表明，大多数外周蛋白质不仅与膜表面相互作用，但渗透通过界面区域，并达到烃的内部，这是与已发表的实验研究一致。
Three-dimensional (3D) structures of numerous peripheral membrane proteins have been determined. Biological activity, stability, and conformations of these proteins depend on their spatial positions with respect to the lipid bilayer. However, these positions are usually undetermined. We report the first large-scale computational study of monotopic/peripheral proteins with known 3D structures. The optimal translational and rotational positions of 476 proteins are determined by minimizing energy of protein transfer from water to the lipid bilayer, which is approximated by a hydrocarbon slab with a decadiene-like polarity and interfacial regions characterized by water-permeation profiles. Predicted membrane-binding sites, protein tilt angles and membrane penetration depths are consistent with spin-labeling, chemical modification, fluorescence, NMR, mutagenesis, and other experimental studies of 53 peripheral proteins and peptides. Experimental membrane binding affinities of peripheral proteins were reproduced in cases that did not involve a helix-coil transition, specific binding of lipids, or a predominantly electrostatic association. Coordinates of all examined peripheral proteins and peptides with the calculated hydrophobic membrane boundaries, subcellular localization, topology, structural classification, and experimental references are available through the Orientations of Proteins in Membranes (OPM) database. Positions of diverse peripheral proteins and peptides in the lipid bilayer can be accurately predicted using their 3D structures that represent a proper membrane-bound conformation and oligomeric state, and have membrane binding elements present. The success of the implicit solvation model suggests that hydrophobic interactions are usually sufficient to determine the spatial position of a protein in the membrane, even when electrostatic interactions or specific binding of lipids are substantial. Our results demonstrate that most peripheral proteins not only interact with the membrane surface, but penetrate through the interfacial region and reach the hydrocarbon interior, which is consistent with published experimental studies.
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DOI：
10.1073/pnas.0510006103
发表时间：
2006-01-24
影响因子：
11.1
作者：
Begley, MJ;Taylor, GS;Dixon, JE
通讯作者：
Dixon, JE
影响因子：
2.9
作者：
Ahn, KW;Sampson, NS
通讯作者：
Sampson, NS
影响因子：
2.9
作者：
Akiba, T;Nishio, M;Harata, K
通讯作者：
Harata, K
影响因子：
3.4
作者：
BenTal, N;Honig, B;McLaughlin, S
通讯作者：
McLaughlin, S
影响因子：
2.9
作者：
Bollinger, JG;Diraviyam, K;Gelb, MH
通讯作者：
Gelb, MH