Nussinov Ruth
Basic Research Program, SAIC-Frederick, Inc. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. Sackler Inst. of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Phys Biol. 2013 Aug;10(4):045004. doi: 10.1088/1478-3975/10/4/045004. Epub 2013 Aug 2.
The spatial structure of the cell is highly organized at all levels: from small complexes and assemblies, to local nano- and microclusters, to global, micrometer scales across and between cells. We suggest that this multiscale spatial cell organization also organizes signaling and coordinates cellular behavior. We propose a new view of the spatial structure of cell signaling systems. This new view describes cell signaling in terms of dynamic allosteric interactions within and among distinct, spatially organized transient clusters. The clusters vary over time and space and are on length scales from nanometers to micrometers. When considered across these length scales, primary factors in the spatial organization are cell membrane domains and the actin cytoskeleton, both also highly dynamic. A key challenge is to understand the interplay across these multiple scales, link it to the physicochemical basis of the conformational behavior of single molecules and ultimately relate it to cellular function. Overall, our premise is that at these scales, cell signaling should be thought of not primarily as a sequence of diffusion-controlled molecular collisions, but instead transient, allostery-driven cluster re-forming interactions.
从小的复合物和组装体，到局部的纳米和微聚集体，再到跨越细胞和细胞之间的全局微米尺度。我们认为这种多尺度的空间细胞组织也会组织信号传导并协调细胞行为。我们提出了一种关于细胞信号系统空间结构的新观点。这种新观点根据不同的、空间组织化的瞬态聚集体内部和之间的动态变构相互作用来描述细胞信号传导。这些聚集体随时间和空间变化，长度尺度从纳米到微米。当从这些长度尺度来考虑时，空间组织的主要因素是细胞膜结构域和肌动蛋白细胞骨架，它们也都是高度动态的。一个关键挑战是理解这些多个尺度之间的相互作用，将其与单分子构象行为的物理化学基础联系起来，并最终将其与细胞功能联系起来。总体而言，我们的前提是在这些尺度上，细胞信号传导不应主要被视为一系列扩散控制的分子碰撞，而应是瞬态的、变构驱动的聚集体重新形成相互作用。
