State Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
PLoS One. 2010 Jan 26;5(1):e8900. doi: 10.1371/journal.pone.0008900.
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.
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械细节理解甚少，特别是在快速突触传递期间。在这里，我们通过使用膜和蛋白质的显式模型的非线性泊松-玻尔兹曼方程系统地评估了 SNARE 复合物、辅助蛋白和融合膜之间的静电力。我们发现，在融合膜之间，SNARE 复合物存在以前未被认识到的、结构上优选的和能量上非常有利的横向取向。这种优选的取向立即提出了一种新颖而简单的突触融合蛋白依赖性膜融合的机械触发机制。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曲率事件，为快速突触小泡融合奠定了基础。总之，我们对 SNARE 及其调节因子的静电分析表明，真核膜融合蛋白存在意想不到的、潜在的新机制。
