Three steps forward, two steps back: mechanistic insights into the assembly and disassembly of the SNARE complex.
Three steps forward, two steps back: mechanistic insights into the assembly and disassembly of the SNARE complex.
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DOI：
10.1016/j.cbpa.2015.10.003
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发表时间：
2015-12
影响因子：
7.8
通讯作者：
Munson M
中科院分区：
文献类型：
--
作者：
Bombardier JP;Munson M
在所有真核细胞类型中，膜融合是一个严格控制的过程。SNARE蛋白家族在胞外和内吞运输途径中融合是必需的。运输囊泡上的SNARE与靶膜上的同源SNARE相互作用，形成一个非常稳定的SNARE复合物，为膜融合提供能量，尽管其机制的许多方面仍然难以捉摸。单分子和高分辨率结构方法的最新进展为SNARE复合物如何组装提供了令人兴奋的新见解，包括组装能量的测量和组装途径中中间体的鉴定。这些技术也是阐明SNARE复合体如何分解的机制细节的关键，包括ATP依赖性α-SNAP/ nsf介导的SNARE复合体分解所需的能量学细节，以及分解机制伴随ATP水解的结构变化。此外，SNARE复合体的形成和拆卸是严格监管的过程；创新的生物化学和生物物理特性加深了我们对这些调节因子如何控制膜融合和胞吐的理解。
Membrane fusion is a tightly controlled process in all eukaryotic cell types. The SNARE family of proteins is required for fusion throughout the exocytic and endocytic trafficking pathways. SNAREs on a transport vesicle interact with the cognate SNAREs on the target membrane, forming an incredibly stable SNARE complex that provides energy for the membranes to fuse, although many aspects of the mechanism remain elusive. Recent advances in single-molecule and high-resolution structural methods provide exciting new insights into how SNARE complexes assemble, including measurements of assembly energetics and identification of intermediates in the assembly pathway. These techniques were also key in elucidating mechanistic details into how the SNARE complex is disassembled, including details of the energetics required for ATP-dependent α-SNAP/NSF-mediated SNARE complex disassembly, and the structural changes that accompany ATP hydrolysis by the disassembly machinery. Additionally, SNARE complex formation and disassembly are tightly regulated processes; innovative biochemical and biophysical characterization has deepened our understanding of how these regulators work to control membrane fusion and exocytosis.