Molecular Simulation of the Effect of Cholesterol on Lipid-Mediated Protein-Protein Interactions
Molecular Simulation of the Effect of Cholesterol on Lipid-Mediated Protein-Protein Interactions
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DOI：
10.1016/j.bpj.2010.09.030
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发表时间：
2010-12-01
影响因子：
3.4
通讯作者：
Smit, Berend
中科院分区：
文献类型：
--
作者：
de Meyer, Frederick J. M.;Rodgers, Jocelyn M.;Smit, Berend
实验和分子模拟表明，蛋白质和膜之间的疏水性错配对脂质介导的蛋白质-蛋白质相互作用有重要贡献。本文讨论了胆固醇对脂质介导的蛋白质-蛋白质相互作用的影响，作为疏水性错配蛋白质直径和蛋白质簇大小、脂质尾长和温度的函数。用混合耗散粒子动力学Monte Carlo方法研究了胆固醇对蛋白质相互作用的影响，提出了胆固醇影响蛋白质相互作用的机理蛋白质诱导的胆固醇富集或胆固醇耗尽的蛋白质周围的脂质壳层影响脂质介导的蛋白质-蛋白质相互作用，计算了蛋白质与蛋白质团簇之间的平均力势，结果表明胆固醇的加入显著降低了蛋白质与蛋白质团簇之间的平均力势具有正错配的蛋白质（蛋白质簇）之间的排斥性脂质介导的相互作用，但不影响具有负错配的蛋白质之间的吸引性相互作用胆固醇对具有不同错配的蛋白质之间的排斥性相互作用仅具有适度的影响
Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid mediated protein protein interactions In this article we discuss the effect of cholesterol on lipid mediated protein protein interactions as function of hydrophobic mismatch protein diameter and protein cluster size lipid tail length and temperature To do so we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded with a hybrid dissipative particle dynamics Monte Carlo method We propose a mechanism by which cholesterol affects protein interactions protein induced cholesterol enriched or cholesterol depleted lipid shells surrounding the proteins affect the lipid mediated protein protein interactions Our calculations of the potential of mean force between proteins and protein clusters show that the addition of cholesterol dramatically reduces repulsive lipid mediated interactions between proteins (protein clusters) with positive mismatch but does not affect attractive interactions between proteins with negative mismatch Cholesterol has only a modest effect on the repulsive interactions between proteins with different mismatch