Tsai Hui-Hsu Gavin, Chang Che-Ming, Lee Jian-Bin
Department of Chemistry, National Central University, Jhong-Li City, Tao-Yuan County 32001, Taiwan.
Department of Chemistry, National Central University, Jhong-Li City, Tao-Yuan County 32001, Taiwan.
Biochim Biophys Acta. 2014 Jun;1838(6):1529-35. doi: 10.1016/j.bbamem.2014.01.018. Epub 2014 Jan 24.
Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
膜融合对于细胞内运输和病毒感染至关重要，但其融合过程背后的分子机制仍知之甚少。在本研究中，我们采用全原子分子动力学模拟，利用预先由囊泡间Ca(2+) - 脂质簇结合的囊泡模型来研究膜融合机制，以近似Ca(2+)催化的融合。我们的结果表明，囊泡融合的半融合隔膜的形成是一个多步骤事件。这一结果与大多数连续介质模型中的假设形成对比。相邻的半融合状态在能量景观上被一个能垒隔开。半融合隔膜比平面脂质双层薄得多。半融合隔膜在形成过程中的变薄导致了囊泡融合的融合孔的打开。这项工作为半融合隔膜的形成提供了新的见解，从而增进了对膜融合分子机制的理解。本文是名为：膜结构与功能：在细胞生理学、病理学和治疗中的相关性的特刊的一部分。
