MOLECULAR EVENTS IN A DISCRETE CYTOPLASMIC SPACE

离散细胞质空间中的分子事件

• 批准号: 6414764
• 负责人: DENNIS BRAY
• 金额: $ 16.2万
• 依托单位: UNIVERSITY OF CAMBRIDGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6414764
• 关键词: Escherichia coli; bacterial proteins; biological signal transduction; carboxylic ester hydrolases; cell membrane; cell morphology; chemotaxis; computer simulation; cytoplasm; intermolecular interaction; membrane structure; methyltransferase; model design /development; molecular dynamics; physical model; protein localization; protein structure function; receptor; receptor expression; statistics /biometry

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.

描述（由申请人提供）：在这个项目中，一个小型且专业的 与趋化受体簇相关的细胞质体积 将详细分析大肠杆菌的表面， 使用计算机建模、随机模拟技术和新颖的 3D 原型技术。受体和相关蛋白质的模型，位于 原子分辨率，将被组装成类似于二维晶格 细菌膜上的受体簇排列一致 具有生化、动力学、突变和行为数据。细胞质的 然后，受体的结构域将用于定义小体积的 质膜下方的细胞质并检查浓度， 与相互作用的“可溶性”酶的分布和扩散行为 受体在适应过程中。两只手的可行性， 酶通过晶格的“臂叉”运动，由于它们拥有 将检查受体的两个相对较弱的结合位点。我们将 还探讨了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，从而导致大规模连贯模式的出现 活动。这项研究的结果可能会提供新颖的见解，而不是 不仅针对细菌趋化性，而且更普遍地还针对其他 膜相关蛋白复合物，例如成纤维细胞中的粘着斑 和脊椎动物中枢神经系统的突触后密度。