An electrostatically preferred lateral orientation of SNARE complex suggests novel mechanisms for driving membrane fusion.
An electrostatically preferred lateral orientation of SNARE complex suggests novel mechanisms for driving membrane fusion.
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SNARE 复合物的静电优先横向取向提出了驱动膜融合的新机制
DOI：
10.1371/journal.pone.0008900
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发表时间：
2010-01-26
期刊：
影响因子：
3.7
通讯作者：
Sui SF
中科院分区：
文献类型：
--
作者：
Guo T;Gong LC;Sui SF
生物膜融合是由SNARE蛋白和其他辅助因子催化的基本细胞过程。然而，SNARE催化的膜融合的关键机制细节知之甚少，特别是在快速突触传递期间。在这里，我们系统地评估了SNARE复合物，辅助蛋白和融合膜之间的静电力的非线性Poisson-Boltzmann方程使用明确的模型的膜和蛋白质。我们发现，一个以前未被认识到的，结构上优选的和积极的高度有利的横向取向存在的SNARE复合物之间的融合膜。这种优选的方向立即表明一种新的和简单的突触结合蛋白依赖性机制触发膜融合。此外，膜、SNARE复合物和辅助蛋白之间的静电相互作用似乎协调了一系列膜弯曲事件，为快速突触囊泡融合奠定了基础。总之，我们对SNARE及其调节因子的静电分析表明了真核细胞膜融合蛋白的意想不到的和潜在的新机制。
Biological membrane fusion is a basic cellular process catalyzed by SNARE proteins and additional auxiliary factors. Yet, the critical mechanistic details of SNARE-catalyzed membrane fusion are poorly understood, especially during rapid synaptic transmission. Here, we systematically assessed the electrostatic forces between SNARE complex, auxiliary proteins and fusing membranes by the nonlinear Poisson-Boltzmann equation using explicit models of membranes and proteins. We found that a previously unrecognized, structurally preferred and energetically highly favorable lateral orientation exists for the SNARE complex between fusing membranes. This preferred orientation immediately suggests a novel and simple synaptotagmin-dependent mechanistic trigger of membrane fusion. Moreover, electrostatic interactions between membranes, SNARE complex, and auxiliary proteins appear to orchestrate a series of membrane curvature events that set the stage for rapid synaptic vesicle fusion. Together, our electrostatic analyses of SNAREs and their regulatory factors suggest unexpected and potentially novel mechanisms for eukaryotic membrane fusion proteins.
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