Stalk model of membrane fusion: Solution of energy crisis

Stalk model of membrane fusion: Solution of energy crisis
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DOI:
10.1016/s0006-3495(02)75450-7
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发表时间:
2002-02-01
影响因子:
3.4
通讯作者:
Kozlov, MM
Kozlov, MM
中科院分区:
生物学3区
文献类型:
--
作者:
Kozlovsky, Y;Kozlov, MM

文献摘要

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膜融合通过形成中间非双层结构进行。聚变中间体的茎模型通常被认为是解释聚变过程的主要现象。然而,以其目前的形式,茎模型构成了一个挑战。一方面,它能够定性地描述膜的脂质组成对融合反应的调节。另一方面,它预测了非常大的茎能量值,因此在生物学上合理的时间跨度内,膜不能克服融合的相关能量障碍。我们提出了一种新的融合柄结构,解决了模型的能量危机。我们的方法是基于茎膜的组合变形,包括膜表面的弯曲和脂质分子的烃链的倾斜。我们证明了聚变柄的能量比以前预测的小几倍,并且在真实的系统中是可行的。我们占定量的实验结果依赖于不同的膜单层的脂质组合物的融合反应。我们分析了茎能量对熔融膜之间的距离的依赖性,并提供了实验可检验的预测的茎中间体的结构特征。
Membrane fusion proceeds via formation of intermediate nonbilayer structures. The stalk model of fusion intermediate is commonly recognized to account for the major phenomenology of the fusion process. However, in its current form, the stalk model poses a challenge. On one hand, it is able to describe qualitatively the modulation of the fusion reaction by the lipid composition of the membranes. On the other, it predicts very large values of the stalk energy, so that the related energy barrier for fusion cannot be overcome by membranes within a biologically reasonable span of time. We suggest a new structure for the fusion stalk, which resolves the energy crisis of the model. Our approach is based on a combined deformation of the stalk membrane including bending of the membrane surface and tilt of the hydrocarbon chains of lipid molecules. We demonstrate that the energy of the fusion stalk is a few times smaller than those predicted previously and the stalks are feasible in real systems. We account quantitatively for the experimental results on dependence of the fusion reaction on the lipid composition of different membrane monolayers. We analyze the dependence of the stalk energy on the distance between the fusing membranes and provide the experimentally testable predictions for the structural features of the stalk intermediates.