Structural Dynamics of Presynaptic Membrane Fusion

突触前膜融合的结构动力学

• 批准号: 8706168
• 负责人: LUKAS K TAMM
• 金额: $ 114.02万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706168
• 关键词: Architecture; Biochemical; Biological; Calcium; Cell membrane; Cells; Complex; Coupling; Defect; Disease; Dissection; Elements; Epilepsy; Evolution; Exocytosis; Instruction; Lead; Membrane Fusion; Mental Depression; Methods; Molecular; Molecular Machines; Neurons; Optics; Process; Proteins; Regulation; Resolution; SNAP receptor; Spectrum Analysis; Structural Biologist; Synapses; Synaptic Transmission; Synaptic Vesicles; Vesicle; base; combat; genetic regulatory protein; mutant; nervous system disorder; presynaptic; programs; structural biology; synaptotagmin

This program project consisting of three projects and three cores ainns at elucidating molecular mechanisms that are responsible for membrane fusion in presynaptic exocytosis. The molecular machine at the center of this process is the SNARE complex that assembles from its components during presynaptic membrane fusion. Energy derived from SNARE complex folding and assembly drives the kinetically blocked fusion of vesicle and cell membrane bilayers. Regulatory proteins including synaptotagmin, complexin, and Munc18 render SNARE complex formation and fusion sensitive to calcium and control SNARE assembly and fusion by mechanisms that are still poorly understood at the structural mechanistic level. A group of talented biochemists, structural biologists, biophysicists, and cell biologists has been asembled in this program project to jointly tackle several key questions of presynaptic membrane fusion. SNARE assembly and fusion intermediates will be structurally and functionally characterized and correlated; the structural and biophysical basis of the regulation of SNARE assembly by accessory proteins and its coupling to fusion will be elucidated; and the evolution of the supramolecular architecture of nascent and mature fusion pores will be examined. The approaches range from high-resolution molecular spectroscopy and structural biology to biochemical and molecular biological dissections of the process with judiciously selected mutants to advanced optical and cell biological methods.

该计划项目由三个项目和三个核心组成，以阐明分子机制 负责突触前胞吐作用的膜融合。中心的分子机 这个过程是在突触前膜期间从其组件组装的圈套复合物 融合。源自军鼓复合物折叠和组装的能量驱动了动力学阻塞的融合 囊泡和细胞膜双层。调节蛋白包括突触蛋白，复合素和Munc18 使军团复合物的形成和融合对钙和控制军鼓组件和融合敏感 通过在结构机械水平上仍然很少理解的机制。一群才华横溢 在该计划中，生物化学家，结构生物学家，生物物理学家和细胞生物学家已被吸引 计划共同解决突触前膜融合的几个关键问题。军鼓装配和 融合中间体将在结构和功能上表征和相关。结构和 辅助蛋白及其与融合的耦合对军鼓组装调节的生物物理基础将 阐明；以及新生和成熟融合孔的超分子结构的演变将 被检查。该方法范围从高分辨率分子光谱和结构生物学到 该过程的生化和分子生物解剖，并明智地选择突变体 晚期光学和细胞生物学方法。