Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, United States.
J Phys Chem B. 2021 Sep 9;125(35):9990-9998. doi: 10.1021/acs.jpcb.1c04905. Epub 2021 Aug 30.
Peripheral membrane proteins bind transiently to membrane surfaces as part of many signaling pathways. The bound proteins perform two-dimensional (2-D) diffusion on the membrane surface during the recruitment function. To better understand the interplay between the 2-D diffusion of these protein domains and their membrane binding modes, we performed multimicrosecond all-atom molecular dynamics simulations of two regulatory domains, a C2 domain and a pleckstrin homology (PH) domain, in their experimentally determined bound configuration to a lipid bilayer. The protein bound configurations are preserved throughout the simulation trajectories. Both protein domains exhibit anomalous diffusion with distinct features in their dynamics that reflect their different modes of binding. An analysis of their diffusive behavior reveals common features with the diffusion of lipid molecules in lipid bilayers, suggesting that the 2-D motion of protein domains bound to the membrane surface is modulated by the viscoelastic nature of the lipid bilayer.
外周膜蛋白作为许多信号通路的一部分，暂时结合在膜表面上。在募集功能期间，结合的蛋白质在膜表面上进行二维（2-D）扩散。为了更好地理解这些蛋白结构域的 2-D 扩散与其膜结合模式之间的相互作用，我们对两个调节结构域（C2 结构域和pleckstrin 同源（PH）结构域）进行了多微秒全原子分子动力学模拟，这些结构域在实验确定的结合构象中存在于脂质双层中。在整个模拟轨迹中，蛋白质的结合构象都得到了保留。两个蛋白结构域都表现出异常扩散，其动力学具有不同的特征，反映了它们不同的结合模式。对它们扩散行为的分析揭示了与脂质双层中脂质分子扩散的共同特征，这表明与膜表面结合的蛋白结构域的 2-D 运动受脂质双层粘弹性的调节。
