Huang William Y C, Chiang Han-Kuei, Groves Jay T
Department of Chemistry, University of California, Berkeley, Berkeley, California.
Department of Chemistry, University of California, Berkeley, Berkeley, California.
Biophys J. 2017 Oct 17;113(8):1807-1813. doi: 10.1016/j.bpj.2017.08.024.
Biochemical signaling pathways often involve proteins with multiple, modular interaction domains. Signaling activates binding sites, such as by tyrosine phosphorylation, which enables protein recruitment and growth of networked protein assemblies. Although widely observed, the physical properties of the assemblies, as well as the mechanisms by which they function, remain largely unknown. Here we examine molecular mobility within LAT:Grb2:SOS assemblies on supported membranes by single-molecule tracking. Trajectory analysis reveals a discrete temporal transition to subdiffusive motion below a characteristic timescale, indicating that the LAT:Grb2:SOS assembly has the dynamical structure of a loosely entangled polymer. Such dynamical analysis is also applicable in living cells, where it offers another dimension on the characteristics of cellular signaling assemblies.
生化信号通路通常涉及具有多个模块化相互作用结构域的蛋白质。信号传导会激活结合位点，比如通过酪氨酸磷酸化，这使得蛋白质能够募集并促进网络化蛋白质组装体的生长。尽管这种现象广泛存在，但这些组装体的物理性质以及它们发挥功能的机制在很大程度上仍然未知。在这里，我们通过单分子追踪研究了支持膜上LAT:Grb2:SOS组装体中的分子流动性。轨迹分析揭示了在一个特征时间尺度以下向亚扩散运动的离散时间转变，这表明LAT:Grb2:SOS组装体具有松散缠结聚合物的动态结构。这种动态分析也适用于活细胞，它为细胞信号组装体的特征提供了另一个维度。
