Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.
Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.
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DOI：
10.1080/10409238.2022.2121804
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发表时间：
2022-08
影响因子：
6.5
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中科院分区：
文献类型：
--
作者：
含有递质的囊泡与突触和神经肌肉接头处的质膜融合，分别介导神经传递和肌肉收缩，从而成为所有思想和行动的基础。融合过程由三种突触SNARE蛋白--靶质膜上的突触融合蛋白-1和SNAP-25（t-SNARE）和囊泡膜上的VAMP 2（v-SNARE）耦合折叠和组装成四螺旋束驱动。它们的组装由Munc 18 -1和许多其他蛋白质陪伴，以实现神经传递所需的速度和准确性。然而，SNARE组装的生理途径及其与膜融合的偶联仍不清楚。在这里，我们回顾了最近的进展，了解陷阱组装和膜融合，重点是通过单分子操作方法和电记录的单融合孔所获得的结果。我们描述了两个途径的突触陷阱组装，其相关的中间体，能量学和动力学。三个SNARE在体外的组装开始于t-SNARE二元复合物的形成，其上VAMP 2以逐步拉链样方式折叠。Munc 18 -1显著改变SNARE组装途径：syntaxin-1和VAMP 2首先结合在Munc 18 -1的表面上形成模板复合物，SNAP-25与该模板复合物结合以结束SNARE组装并取代Munc 18 -1。在膜融合过程中，多个trans-SNARE复合物以依赖于它们的拷贝数和拉链状态的方式合作打开动态融合孔。总之，这些结果表明，逐步和合作SNARE组装驱动分阶段的膜融合。
Fusion of transmitter-containing vesicles with plasma membranes at the synaptic and neuromuscular junctions mediates neurotransmission and muscle contractions, respectively, thereby underlying all thoughts and actions. The fusion process is driven by the coupled folding and assembly of three synaptic SNARE proteins - syntaxin-1 and SNAP-25 on the target plasma membrane (t-SNAREs) and VAMP2 on the vesicular membrane (v-SNARE) into a four-helix bundle. Their assembly is chaperoned by Munc18–1 and many other proteins to achieve the speed and accuracy required for neurotransmission. However, the physiological pathway of SNARE assembly and its coupling to membrane fusion remain unclear. Here, we review recent progress in understanding SNARE assembly and membrane fusion, with a focus on results obtained by single-molecule manipulation approaches and electric recordings of single fusion pores. We describe two pathways of synaptic SNARE assembly, their associated intermediates, energetics, and kinetics. Assembly of the three SNAREs in vitro begins with the formation of a t-SNARE binary complex, on which VAMP2 folds in a stepwise zipper-like fashion. Munc18–1 significantly alters the SNARE assembly pathway: syntaxin-1 and VAMP2 first bind on the surface of Munc18–1 to form a template complex, with which SNAP-25 associates to conclude SNARE assembly and displace Munc18–1. During membrane fusion, multiple trans-SNARE complexes cooperate to open a dynamic fusion pore in a manner dependent upon their copy number and zippering states. Together, these results demonstrate that stepwise and cooperative SNARE assembly drive stagewise membrane fusion.
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影响因子：
64.8
作者：
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