MOLECULAR EVENTS IN A DISCRETE CYTOPLASMIC SPACE

描述(申请人提供)：在这个项目中，一个小型的和专业的 与一簇趋化受体相关的细胞质体积 我们将非常详细地分析细菌大肠杆菌的表面， 使用计算机建模、随机模拟技术和一种新的3D 原型技术。受体和相关蛋白质的模型，在 原子分辨率，将组装成一个类似于 细菌膜上一致排列的受体簇 生化、动力学、突变和行为数据。细胞质 然后，受体的结构域将被用来定义一小部分 质膜下的细胞质，并检测其浓度， 与之相互作用的“可溶性”酶的分布和扩散行为 适应过程中的受体。双手操作的可行性， 酶通过晶格的“臂状”运动，这是由于它们拥有 将检查受体的两个相对较弱的结合部位。我们会 也探索构象变化可能的理论可能性 通过干预，从一个受体传播到晶格中的相邻受体 蛋白质，从而导致大规模相干模式的出现 活动。这项研究的结果可能会提供新的见解 不仅是细菌的趋化性，更广泛地说，也是对其他 膜相关蛋白复合体，如成纤维细胞中的局灶性粘连 以及脊椎动物中枢神经系统中突触后的密度。

DESCRIPTION (provided by applicant): In this project, a small and specialized volume of cytoplasm associated with a cluster of chemotactic receptors on the surface of the bacterium Escherichia coli will be analyzed in great detail, using computer modeling, stochastic simulation techniques, and a novel 3D prototyping technique. Models of the receptors and associated proteins, at atomic resolution, will be assembled into a two-dimensional lattice resembling the cluster of receptors in the bacterial membrane in an arrangement consistent with biochemical, kinetic, mutational and behavioral data. The cytoplasmic domains of the receptors will then be used to define a small volume of cytoplasm subjacent to the plasma membrane and to examine the concentrations, distributions and diffusive behavior of "soluble" enzymes that interact with the receptors in the course of adaptation. The feasibility of a two-handed, "brachiation" motion of enzymes through the lattice, due to their possession of two relatively weak binding sites for the receptors will be examined. We will also explore the theoretical possibility that conformational changes might spread, from one receptor to its neighbors in the lattice via intervening proteins, and thereby lead to the emergence of large-scale coherent patterns of activity. The results of this study are likely to provide novel insight not only on bacterial chemotaxis but also, more generally, on other membrane-associated protein complexes, such as focal adhesions in fibroblasts and postsynaptic densities in the vertebrate central nervous system.