Corradi Valentina, Mendez-Villuendas Eduardo, Ingólfsson Helgi I, Gu Ruo-Xu, Siuda Iwona, Melo Manuel N, Moussatova Anastassiia, DeGagné Lucien J, Sejdiu Besian I, Singh Gurpreet, Wassenaar Tsjerk A, Delgado Magnero Karelia, Marrink Siewert J, Tieleman D Peter
Centre for Molecular Simulation and Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada.
Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
ACS Cent Sci. 2018 Jun 27;4(6):709-717. doi: 10.1021/acscentsci.8b00143. Epub 2018 Jun 13.
Cell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Our current understanding of the detailed organization of cell membranes remains rather elusive, because of the challenge to study fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of 10 different membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between the leaflets. The simulations detail how each protein modulates its local lipid environment in a unique way, through enrichment or depletion of specific lipid components, resulting in thickness and curvature gradients. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far-reaching implications for our understanding of the overall organization of real cell membranes.
细胞膜以不对称的排列方式包含数百种不同的蛋白质和脂质。由于难以在所需的时空分辨率下研究脂质和蛋白质波动的纳米级组装体，我们目前对细胞膜详细组织的理解仍然相当模糊。在这里，我们使用分子动力学模拟来表征10种不同膜蛋白的脂质环境。为了提供一个真实的脂质环境，这些蛋白质被嵌入到一个模型质膜中，其中有60多种脂质种类，在小叶之间不对称分布。模拟详细展示了每种蛋白质如何通过富集或消耗特定脂质成分，以独特的方式调节其局部脂质环境，从而产生厚度和曲率梯度。我们的结果提供了脂质-蛋白质相互作用复杂性的分子视角，对我们理解真实细胞膜的整体组织可能具有深远影响。
