MOLECULAR EVENTS IN A DISCRETE CYTOPLASMIC SPACE

描述（由申请人提供）：在这个项目中，一个小型和专业的 细胞质体积与细胞表面的趋化受体簇相关， 将详细分析大肠杆菌的表面， 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的模型， 原子分辨率，将被组装成一个二维晶格， 细菌膜中的受体簇排列一致 生化动力学突变和行为数据细胞质 然后将受体的结构域用于限定小体积的 细胞质贴附于质膜并检查浓度， 分布和扩散行为的“可溶性”酶，相互作用， 在适应过程中的感受器。一个双手， 酶通过晶格的“臂化”运动，由于它们拥有 将检查受体的两个相对弱的结合位点。我们将 也探索了构象变化可能 扩散，从一个受体到它的邻居在晶格中通过干预 蛋白质，从而导致出现大规模的连贯模式， 活动这项研究的结果可能会提供新的见解， 不仅对细菌的趋化性，而且更普遍地，对其他 膜相关蛋白复合物，如成纤维细胞中的局灶性粘连 和脊椎动物中枢神经系统中的突触后密度。

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.