Yamamoto Eiji, Kalli Antreas C, Akimoto Takuma, Yasuoka Kenji, Sansom Mark S P
Department of Mechanical Engineering, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom.
Sci Rep. 2015 Dec 14;5:18245. doi: 10.1038/srep18245.
Pleckstrin homology (PH) domains are lipid-binding modules present in peripheral membrane proteins which interact with phosphatidyl-inositol phosphates (PIPs) in cell membranes. We use multiscale molecular dynamics simulations to characterize the localization and anomalous dynamics of the DAPP1 PH domain on the surface of a PIP-containing lipid bilayer. Both translational and rotational diffusion of the PH domain on the lipid membrane surface exhibit transient subdiffusion, with an exponent α ≈ 0.5 for times of less than 10 ns. In addition to a PIP3 molecule at the canonical binding site of the PH domain, we observe additional PIP molecules in contact with the protein. Fluctuations in the number of PIPs associated with the PH domain exhibit 1/f noise. We suggest that the anomalous diffusion and long-term correlated interaction of the PH domain with the membrane may contribute to an enhanced probability of encounter with target complexes on cell membrane surfaces.
普列克底物蛋白同源（PH）结构域是外周膜蛋白中存在的脂质结合模块，可与细胞膜中的磷脂酰肌醇磷酸（PIP）相互作用。我们使用多尺度分子动力学模拟来表征含PIP的脂质双层表面上DAPP1 PH结构域的定位和反常动力学。PH结构域在脂质膜表面的平移扩散和旋转扩散均表现出瞬态亚扩散，对于小于10 ns的时间，指数α≈0.5。除了在PH结构域的典型结合位点处有一个PIP3分子外，我们还观察到与该蛋白接触的其他PIP分子。与PH结构域相关的PIP数量波动表现出1/f噪声。我们认为，PH结构域与膜的反常扩散和长期相关相互作用可能有助于提高在细胞膜表面与靶复合物相遇的概率。
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