Department of Physiology, University of Wisconsin, Madison, USA.
J Membr Biol. 2010 Jun;235(2):89-100. doi: 10.1007/s00232-010-9258-1. Epub 2010 May 30.
The assembly of SNARE proteins into a tight complex has been hypothesized to drive membrane fusion. A model of the initial fusion pore as a proteinaceous channel formed by SNARE proteins places their membrane anchors in separate membranes. This leaves the possibility of a final assembly step that brings the membrane anchors together and drives fusion pore expansion. The present study develops a model for expansion in which the final SNARE complex zipping step drives a transition from a proteinaceous fusion pore to a lipidic fusion pore. An estimate of the energy released upon merger of the helical segments of the SNARE motifs with the helical segments of the membrane anchors indicates that completing the assembly of a few SNARE complexes can overcome the elastic energy that opposes lipid bilayer deformation into a narrow fusion pore. The angle between the helical axes of the membrane anchor and SNARE motif serves as a useful reaction coordinate for this transition. Energy was calculated as a function of this angle, incorporating contributions from membrane bending, SNARE complex assembly, membrane anchor flexing and hydrophobic interactions. The rate of this transition was evaluated as a process of diffusion over the barrier imposed by these combined energies, and the rates estimated were consistent with experimental measurements.
已假设 SNARE 蛋白的组装成紧密复合物会驱动膜融合。最初融合孔的模型被认为是由 SNARE 蛋白形成的蛋白通道，其膜锚定在不同的膜上。这留下了最终组装步骤的可能性，该步骤将膜锚定在一起并驱动融合孔扩张。本研究提出了一种扩展模型，其中最终的 SNARE 复合物拉链步骤驱动从蛋白融合孔到脂融合孔的转变。对 SNARE 模体的螺旋片段与膜锚定的螺旋片段合并时释放的能量的估计表明，完成几个 SNARE 复合物的组装可以克服阻碍脂质双层变形为狭窄融合孔的弹性能量。膜锚定和 SNARE 模体的螺旋轴之间的夹角可作为此转变的有用反应坐标。根据该角度计算了能量，其中包括膜弯曲、SNARE 复合物组装、膜锚定弯曲和疏水相互作用的贡献。该转变的速率被评估为通过这些组合能量施加的势垒的扩散过程，估计的速率与实验测量值一致。
