Bacterial Mechanisms for Establishing and Maintaining Cell Polarity

建立和维持细胞极性的细菌机制

• 批准号: 9315903
• 负责人: Grant Robert Bowman
• 金额: $ 20.54万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315903
• 关键词: Address; Affinity; Alphaproteobacteria; Anatomy; Area; Bacteria; Binding; Binding Proteins; Caulobacter; Caulobacter crescentus; Cell Cycle; Cell Cycle Regulation; Cell Polarity; Cell Wall; Cell physiology; Cells; Chromosome Segregation; Cues; Cytoplasm; Diffusion; Disease; Feedback; Goals; Growth; In Vitro; Infection; Investigation; Kinetics; Knowledge; Learning; Life; Link; Location; Measures; Mechanics; Membrane; Microbial Biofilms; Modeling; Molecular; Morphology; Multiprotein Complexes; Outcome; Pathogenicity; Polymers; Process; Prokaryotic Cells; Property; Proteins; Research; Role; Scaffolding Protein; Series; Signal Transduction; Signaling Protein; Specificity; Structure; Testing; Time; Virulence; biophysical analysis; biophysical model; cell growth; cell motility; cell type; experimental study; pathogen; pathogenic bacteria; polarized cell; programs; protein complex; residence; retinal rods; scaffold

PROJECT SUMMARY Many rod-shaped bacteria are polarized, meaning that one end of the cell is morphologically and functionally distinct from the other, but there is a general lack of understanding of the mechanisms by which polar asymmetry is established and maintained. Since polarized features provide critical spatial cues for many processes, including chromosome segregation and cell growth, learning the molecular basis for this `bacterial anatomy' will provide fundamental advancements in prokaryotic cell physiology. Furthermore, some pathogenic bacteria use cell polarity to create multiple cell types with specialized roles in supporting virulence. Understanding cell polarity in this context may therefore provide fundamental discoveries relating to core mechanisms for bacterial pathogenicity. What keeps the poles in a state of disequilibrium? This project focuses on the molecular mechanisms that control the interactions between polar proteins and a polar organizing protein, called PopZ, which forms polymeric scaffolds at both cell poles in Caulobacter crescentus. The approach extends from the surprising discovery that PopZ is a molecular hub that organizes the cell by directly interacting with a large number of binding partners. This implies that there is a selection mechanism that supports two parallel programs for PopZ-dependent multiprotein complex assembly at opposite ends of the cell. The proposal includes a series of experiments that will elucidate the selection mechanism. Using a group of established PopZ binding partners, structural and biophysical analyses will be used to understand binding and binding kinetics at the atomic scale. An area of particular focus will be an intrinsically disordered region within PopZ that determines binding specificity. These experiments will provide critical information in developing a detailed biophysical model of hub network assembly and function. The second aim is to test different models for establishing and maintaining polarity in Caulobacter. One possibility is that stable binding partners are used to mark an `old' pole, another is that each pole has a different set of signaling proteins that reinforce polarity through signal feedback loops.

项目摘要 许多棒状细菌是极化的，这意味着细胞的一端是 在形态和功能上与另一个不同，但普遍缺乏 了解建立极性不对称的机制和 维护。由于极化功能为许多过程提供了关键的空间提示，因此 包括染色体分离和细胞生长，学习分子基础 “细菌解剖学”将在原核细胞中提供基本进步 生理。此外，某些致病细菌使用细胞极性产生多个 在支持毒力方面具有专门作用的细胞类型。了解细胞极性 因此，这种情况可能会提供与核心机制有关的基本发现 用于细菌致病性。 是什么使两极保持不平衡状态？该项目着重于分子 控制极性蛋白与极性组织之间相互作用的机制 蛋白质称为popz，它在花​​椰菜中的两个细胞杆上形成聚合物支架 新月。该方法从令人惊讶的发现是popz是一个分子 通过直接与大量绑定进行相互作用来组织电池的集线器 合作伙伴。这意味着有一种选择机制支持两个平行 依赖popz的多蛋白复合物组件的程序 细胞。 该提案包括一系列实验，以阐明选择 机制。使用一组已建立的波普兹结合伙伴，结构和 生物物理分析将用于理解结合和结合动力学 原子量表。特别重点的区域将是一个内在无序的区域 决定结合特异性的POPZ。这些实验将提供关键 开发集线器网络组件的详细生物物理模型的信息 功能。第二个目的是测试建立和维护的不同模型 花椰菜中的极性。一种可能性是稳定的绑定伙伴用于标记 一个“老”杆，另一个是每个杆都有不同的信号蛋白 通过信号反馈回路增强极性。