Reddy Tyler, Shorthouse David, Parton Daniel L, Jefferys Elizabeth, Fowler Philip W, Chavent Matthieu, Baaden Marc, Sansom Mark S P
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique, UPR9080, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Structure. 2015 Mar 3;23(3):584-597. doi: 10.1016/j.str.2014.12.019. Epub 2015 Feb 19.
The influenza virus is surrounded by an envelope composed of a lipid bilayer and integral membrane proteins. Understanding the structural dynamics of the membrane envelope provides biophysical insights into aspects of viral function, such as the wide-ranging survival times of the virion in different environments. We have combined experimental data from X-ray crystallography, nuclear magnetic resonance spectroscopy, cryo-electron microscopy, and lipidomics to build a model of the intact influenza A virion. This is the basis of microsecond-scale coarse-grained molecular dynamics simulations of the virion, providing simulations at different temperatures and with varying lipid compositions. The presence of the Forssman glycolipid alters a number of biophysical properties of the virion, resulting in reduced mobility of bilayer lipid and protein species. Reduced mobility in the virion membrane may confer physical robustness to changes in environmental conditions. Our simulations indicate that viral spike proteins do not aggregate and thus are competent for multivalent immunoglobulin G interactions.
流感病毒被一层由脂质双层和整合膜蛋白组成的包膜所包围。了解膜包膜的结构动力学为病毒功能的各个方面提供了生物物理学见解，例如病毒粒子在不同环境中的广泛存活时间。我们结合了来自X射线晶体学、核磁共振光谱、冷冻电子显微镜和脂质组学的实验数据，构建了完整甲型流感病毒粒子的模型。这是对病毒粒子进行微秒级粗粒度分子动力学模拟的基础，可在不同温度和不同脂质组成下进行模拟。福斯曼糖脂的存在改变了病毒粒子的许多生物物理特性，导致双层脂质和蛋白质种类的流动性降低。病毒粒子膜中流动性的降低可能赋予其对环境条件变化的物理稳健性。我们的模拟表明，病毒刺突蛋白不会聚集，因此能够进行多价免疫球蛋白G相互作用。
