Insertion and assembly of membrane proteins via simulation.
Insertion and assembly of membrane proteins via simulation.
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DOI：
10.1021/ja0569104
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发表时间：
2006-03-01
影响因子：
15
通讯作者：
Sansom MS
中科院分区：
文献类型：
--
作者：
Bond PJ;Sansom MS
脂质的相互作用对膜蛋白的折叠和稳定性至关重要。粗粒度分子模拟已被用于揭示蛋白质/膜和蛋白质/去污剂复合物的两类膜蛋白，即血型糖蛋白（简单的α-螺旋束）和OmpA（β-桶）的代表的自组装机制。粗粒度的模拟的准确性建立通过比较与蛋白质/洗涤剂胶束的自组装的等效原子模拟。OmpA/双层自组装的模拟揭示了折叠的外膜蛋白如何插入双层中。血型糖蛋白/双层模拟支持膜折叠的两态模型，其中跨膜螺旋插入先于双层内的二聚体自组装。模拟还表明，在双层内的血型糖蛋白螺旋单体和二聚体之间存在动态平衡。模拟的血型糖蛋白螺旋二聚体的结构非常接近NMR所揭示的结构。因此，粗粒度的方法可能有助于定义膜蛋白（重）折叠的机制，并将证明适合于模拟更大规模的生物膜的动态重排。
Interactions of lipids are central to the folding and stability of membrane proteins. Coarse-grained molecular simulations have been used to reveal the mechanisms of self-assembly of protein/membrane and protein/detergent complexes for representatives of two classes of membrane protein, namely glycophorin (a simple α-helical bundle) and OmpA (a β-barrel). The accuracy of the coarse-grained simulations is established via comparison with the equivalent atomistic simulations of self-assembly of protein/detergent micelles. The simulation of OmpA/bilayer self-assembly reveals how a folded outer membrane protein can be inserted in a bilayer. The glycophorin/bilayer simulation supports the two-state model of membrane folding, in which transmembrane helix insertion precedes dimer self-assembly within a bilayer. The simulations also suggest a dynamic equilibrium exists between the glycophorin helix monomer and dimer within a bilayer. The simulated glycophorin helix dimer is remarkably close in structure to that revealed by NMR. Thus, coarse-grained methods may help to define mechanisms of membrane protein (re)folding, and will prove suitable for simulation of larger scale dynamic rearrangements of biological membranes.