Division of Medicinal Chemistry and Pharmacognosy, Biophysics Graduate Program, Translational Data Analytics Institute , The Ohio State University , Columbus , Ohio 43210 , United States.
UT/ORNL Center for Molecular Biophysics, Biosciences Division , Oak Ridge National Laboratory , Oak Ridge , Tennessee 37831-6309 , United States.
Chem Rev. 2019 May 8;119(9):5849-5880. doi: 10.1021/acs.chemrev.8b00439. Epub 2019 Feb 12.
To execute their many vital functions, cell membranes are highly organized. Here, we review how membrane structure shapes signal transduction across membranes. Recent experimental and computational advances have shed significant light on mechanisms linking the function of membrane signaling proteins to the composition and physical properties of the membrane lateral structures in which they are embedded. We provide an overview of the structural characteristics of membranes containing heterogeneous mixtures of lipids and other molecules and summarize work on "raft" domains in model and cell membranes, as determined by microscopy, spectroscopy, neutron scattering, and computer simulations. We discuss the principles of partitioning of proteins into membranes and how the structure, dynamics, and function of membrane-embedded and peripheral proteins can be modulated by specific membrane components and physical properties of membranes and raft domains. Finally, we discuss challenges and future directions toward a molecular-level understanding of how membrane organization gives rise to various context-dependent cellular signaling.
为了执行其众多重要功能，细胞膜具有高度的组织性。在这里，我们回顾了膜结构如何在跨膜信号转导中发挥作用。最近的实验和计算进展极大地揭示了将膜信号转导蛋白的功能与它们所嵌入的膜横向结构的组成和物理性质联系起来的机制。我们概述了含有脂质和其他分子的不均匀混合物的膜的结构特征，并总结了通过显微镜、光谱学、中子散射和计算机模拟在模型和细胞膜中“筏”域的工作。我们讨论了蛋白质分配到膜中的原理，以及膜嵌入蛋白和周边蛋白的结构、动态和功能如何被特定的膜成分和膜及筏域的物理性质所调节。最后，我们讨论了在分子水平上理解膜组织如何产生各种依赖于环境的细胞信号的挑战和未来方向。
