The mechanisms of lipid-protein rearrangements during viral infection
The mechanisms of lipid-protein rearrangements during viral infection
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DOI：
10.1016/j.bioelechem.2003.10.016
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发表时间：
2004-06-01
影响因子：
5
通讯作者：
Chizmadzhev, YA
中科院分区：
文献类型：
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作者：
Chizmadzhev, YA
膜融合和裂变是活细胞功能中的重要事件。尽管有各种各样的具体情况，但所有这些现象很可能都受到相同的物理原理的支配。通过对模型脂质系统的研究，首次深入了解了膜融合的物理学。这些结果为后续生物融合机制的研究奠定了基础。这篇简短的综述的主要目的是揭示这些研究道路上的里程碑，并讨论问题和前景。融合是一个多阶段的过程，包括几个中间体之间的过渡。在两个平面双层膜融合的情况下，经历了以下几个阶段：形成紧密的膜间接触，出现称为茎的局部单层桥，茎的膨胀导致半融合膜(HD)的形成，最终形成融合孔。请注意，茎是纳米级的，仍然是一个看不见的物体。然而，毫无疑问，在其形状和结构、能量和动力学性质尚不清楚的情况下，某些类型的单层桥的存在是毋庸置疑的。在表达流感病毒血凝素(HA)融合蛋白的细胞上取得了关于生物融合机制的主要结果。然而，这个系统没有流感的M1和M2蛋白，这两种蛋白负责将病毒的遗传物质释放到靶细胞中。我们实验室开发的一个实验系统可以监测单个病毒粒子与脂质双层的融合，并检测RNA的释放以及M1和M2在这一过程中的作用。生物融合是脂类和特殊蛋白质在纳米范围内复杂相互作用的结果。似乎蛋白质的第一个功能是准备一种预融合状态，也称为膜对接。蛋白质和脂类之间的能量重新分配导致了所谓的韧窝的产生，这些韧窝积累了弯曲能量，从而促进了茎的形成。蛋白质可能会在一系列下坡构象变化的过程中参与随后的融合阶段。不幸的是，关于这些转变的动力学数据是不可用的。因此，理论分析受限于对脂质子系统的考虑，而蛋白质作为边界条件或一些叠加约束参与其中。因此，考虑到脂质的倾斜和融合孔的压缩，提出了从改性秸秆直接通向孔的低能途径。(C)2004爱思唯尔B.V.保留所有权利。
Membrane fusion and fission are important events in living cell functioning. In spite of the great variety of specific cases, all of these phenomena are probably governed by the same physical principles. The first insight into physics of membrane fusion has been achieved through studies on model lipid systems. These results served as a base for subsequent investigations of the mechanisms of biological fusion. The main objective of this brief review is to expose the landmarks on the pathway of these studies and to discuss problems and perspectives.Fusion is a multistage process that includes transitions between several numbers of the intermediates. It is adopted that in the case of fusion of two planar bilayers, the following stages take place: formation of close inter-membrane contact, appearance of local monolayer bridge called a stalk, expansion of stalk leading to formation of hemifusion diaphragm (HD) and, finally, creation of fusion pore. Note that the stalk is nanoscopic and still an invisible object. However, there are no doubts that some kinds of monolayer bridge exist while its shape and structure, energetic and kinetic properties are unknown.The main results on the mechanism of biological fusion were obtained on the cells expressing fusion protein of influenza virus, hemagglutinin (HA). However, this system has no M1 and M2 proteins of influenza, which are responsible for the release of the genetic material of the virus into the target cell. An experimental system developed in our laboratory allows to monitor the fusion of single virions with lipid bilayer and detect RNA release as well as the role of M1 and M2 in this process.Biological fusion is a result of complicated interplay of lipids and special proteins at nanoscopic range. It seems probable that the first function of the proteins is the preparation of a pre-fusion state also known as membrane docking. Redistribution of the energy between proteins and lipids leads to the creation of so-called dimples accumulating bending energy, which facilitates stalk formation. Probably, proteins participate in the subsequent stages of fusion in the course of a set of downhill conformational changes. Unfortunately, the data on the kinetics of these transitions are not available. Therefore, theoretical analysis is limited by a consideration of lipidic subsystem, while proteins participate as boundary conditions or some superimposed constraints. As a result, taking into account lipid tilting and fusion pore compression, low-energy pathway was proposed, leading directly from modified stalk to pore. (C) 2004 Elsevier B.V. All rights reserved.