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.

该项目由三个项目和三个核心组成，旨在阐明分子机制 负责突触前胞吐作用中的膜融合。位于宇宙中心的分子机器 这一过程是SNARE复合体，在突触前膜的过程中， 核聚变来自SNARE复合物折叠和组装的能量驱动了 囊泡和细胞膜双层。调节蛋白包括突触结合蛋白、复合蛋白和Munc 18 使SNARE复合物的形成和融合对钙敏感，并控制SNARE的组装和融合 在结构机制层面上，我们对这些机制仍然知之甚少。一群才华横溢的 生物化学家、结构生物学家、生物化学家和细胞生物学家都参加了这个项目 共同解决突触前膜融合的几个关键问题。SNARE组件和 融合中间体将在结构和功能上进行表征和关联;结构和功能特性将被描述。 通过辅助蛋白调节SNARE组装及其与融合的偶联的生物物理基础将 得到阐明;新生和成熟融合孔的超分子结构的演变将 接受检查。这些方法包括高分辨率分子光谱学和结构生物学， 生物化学和分子生物学解剖的过程与明智选择的突变体， 先进的光学和细胞生物学方法。