Atomic structures of chemotaxis receptors and complexes

趋化受体和复合物的原子结构

• 批准号: 7354271
• 负责人: SUNG-HOU KIM
• 金额: $ 38.34万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-07 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354271
• 关键词: 3-Dimensional; Accounting; Address; Architecture; Bacteria; Bacterial Proteins; Behavior; Cell physiology; Cells; Chemicals; Chemotaxis; Classification; Complex; Cytoplasmic Tail; Detection; Escherichia coli; Foundations; Future; Individual; Infection; Knowledge; Length; Ligand Binding Domain; Methods; Methylation; Molecular; Molecular Conformation; Organism; Play; Principal Investigator; Process; Property; Proteins; Protocols documentation; Receptor Signaling; Role; Signal Transduction; Signal Transduction Pathway; Structure; System; Techniques; Transmembrane Domain; cell motility; dimer; man; mutant; novel therapeutic intervention; pathogen; programs; receptor; structural genomics; transmission process

DESCRIPTION (provided by applicant): The movement of cells and organisms toward or away from chemicals, chemotaxis, is a crucial behavior for their survival that requires sensitive information detection and processing processes. Bacterial chemotactic behavior has been intensively studied for nearly 40 years and is one of the best understood signal transduction systems. Moreover, the molecular mechanisms that enable bacteria to detect chemical gradients with extraordinary sensitivity and range may operate also in more complex organisms. A large body of information is available for individual component proteins of bacterial chemotaxis systems, but some of the most important key information is missing for a complete or near-complete understanding of the molecular mechanisms of the cellular processes of the systems at an atomic level. One of the key missing information is structural information, such as 3-D atomic structures of chemotaxis receptors and their complexes. The specific aims of this proposal are to obtain the 3-D atomic structural information of wild type E. coli chemotaxis receptors and their complexes as well as mutant counterparts locked in signal on or off state. The missing key structural information combined with existing and future dynamic information may lay a foundation for quantitative understanding of molecular mechanisms of cellular processes of the chemotaxis system, for conceptual understanding of signaling systems in higher organisms including man, and for leading to new therapeutic approaches against bacterial pathogens, many of which employ motility and chemotaxis during the infection process.

描述（由申请人提供）：细胞和生物体朝向或远离化学物质的运动，即趋化性，是其生存的关键行为，需要敏感的信息检测和处理过程。细菌趋化行为已经被深入研究了近40年，并且是最好理解的信号转导系统之一。此外，使细菌能够以非凡的灵敏度和范围检测化学梯度的分子机制也可以在更复杂的生物体中发挥作用。 大量的信息可用于细菌趋化性系统的单个组分蛋白质，但一些最重要的关键信息缺失，无法在原子水平上完整或接近完整地理解系统细胞过程的分子机制。其中一个关键的缺失信息是结构信息，如趋化性受体及其复合物的3-D原子结构。该方案的具体目标是获得野生型E的三维原子结构信息。大肠杆菌趋化性受体及其复合物以及突变体对应物锁定在信号开或关状态。 缺失的关键结构信息与现有和未来的动态信息相结合，可能为定量了解趋化系统的细胞过程的分子机制奠定基础，为概念上理解包括人类在内的高等生物体中的信号传导系统奠定基础，并为针对细菌病原体的新治疗方法奠定基础，其中许多病原体在感染过程中采用运动性和趋化性。