Structural Dynamics of Presynaptic Membrane Fusion

该项目由三个项目和三个核心组成，致力于阐明分子机制。 在突触前胞吐中负责膜融合的基因。处于中心的分子机器 这一过程是在突触前膜期间由其组件组装而成的陷阱复合体 核聚变。来自SNARE复合体折叠和组装的能量驱动着动能受阻的融合 囊泡和细胞膜双层。包括突触素、复合蛋白和Munc18在内的调节蛋白 使圈套复合体的形成和融合对钙敏感，并控制圈套的组装和融合 通过在结构机械论层面上仍然知之甚少的机制。一群有才华的人 生物化学家、结构生物学家、生物物理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的项目。诱捕组件和 聚变中间体将在结构和功能上进行表征和关联；结构和 辅助蛋白调节圈套组装及其与融合意志偶联的生物物理基础 新生和成熟融合毛孔的超分子结构的进化将被阐明 接受检查。这些方法从高分辨率分子光谱学和结构生物学到 生化和分子生物学过程的解剖与精心挑选的突变体 先进的光学和细胞生物学方法。

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.