Pre-transition effects mediate forces of assembly between transmembrane proteins.
Pre-transition effects mediate forces of assembly between transmembrane proteins.
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DOI：
10.7554/elife.13150
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发表时间：
2016-02-24
期刊：
影响因子：
7.7
通讯作者：
Chandler D
中科院分区：
文献类型：
--
作者：
Katira S;Mandadapu KK;Vaikuntanathan S;Smit B;Chandler D
我们提出了一种通用的、强大的跨膜蛋白在脂质双层中组装和移动的机制。这种力是膜中有序相和无序相之间的一级相变的预相变(或预熔)效应。通过大规模分子模拟，我们发现疏水厚度等于有序双层中无序相厚度的蛋白质可以稳定微观有序-无序界面。该界面的刚度是有限的。当两个这样的蛋白质相互靠近时，它们会聚集在一起，因为组装减少了净界面能。与疏水效应类似，我们将这种现象称为“有序疏水效应”。这种效应是通过接近有序-无序相变以及蛋白质的大小和疏水失配来实现的。这种效应产生的力的强度和范围明显大于所考虑的膜的膜弹性所产生的力的强度和范围。DOI：http://dx.doi.org/10.7554/eLife.13150.001细胞周围的膜提供了一种选择性屏障，允许一些分子通过，但阻止其他分子的路径。细胞膜由两层分子组成，分子的尾巴是油性的，因此被称为双层。许多蛋白质分布在双层的内外表面：一些蛋白质作为通道控制细胞进出细胞，而另一些蛋白质则突出在细胞外，这样它们就可以感觉到环境的变化。膜蛋白可以在双层内移动和相互作用，各种模型已经出现，试图解释这个动态系统。这些模型基于膜具有一定的流动性，但也具有更多结构的区域，通常将蛋白质描述为漂浮在原本无序的流体膜中的有序簇。然而，许多研究人员现在认为，一些穿过双层的蛋白质(即跨膜蛋白质)使膜更有序，可能是凝胶状态。然而，目前还不清楚跨膜蛋白如何在这样一个相对坚硬的膜内移动和组装在一起。为了调查这一点，Katira，Mandada u，Vaikuntanathan等人。使用简单双层膜的模型进行了计算机模拟。这种膜可以以有序的状态存在，其中油污的尾巴整齐地排列，或者以无序的状态存在，其中它们被不规则地包装。薄膜的虚拟“加热”使其从有序状态转变为无序状态。当将有利于无序状态的简单跨膜蛋白插入到模型膜的有序状态中时，在蛋白质周围局部形成无序区域，并且蛋白质能够在膜内扩散。对两个跨膜蛋白相互靠近时会发生什么的模拟表明，有序-无序转变的一个结果是将蛋白质组装在一起的强大吸引力。Katira，Mandadu，Vaikuntanathan等人。他们将这一新现象命名为“秩序恐惧症”。这种效应产生的力比目前认为的有助于膜蛋白复合体组装的力要大得多，例如由膜的弹性产生的力。这意味着有序恐惧症可能是产生细胞膜中常见的蛋白质簇的原因。下一步的工作应该是探索相反的效果，即将有利于有序状态的蛋白质插入到膜的无序状态中。这预计会导致这些蛋白质聚集，从而在原本无序的膜上形成大的有序区域。DOI：http://dx.doi.org/10.7554/eLife.13150.002
We present a mechanism for a generic, powerful force of assembly and mobility for transmembrane proteins in lipid bilayers. This force is a pre-transition (or pre-melting) effect for the first-order transition between ordered and disordered phases in the membrane. Using large-scale molecular simulation, we show that a protein with hydrophobic thickness equal to that of the disordered phase embedded in an ordered bilayer stabilizes a microscopic order–disorder interface. The stiffness of that interface is finite. When two such proteins approach each other, they assemble because assembly reduces the net interfacial energy. Analogous to the hydrophobic effect, we refer to this phenomenon as the 'orderphobic effect'. The effect is mediated by proximity to the order–disorder phase transition and the size and hydrophobic mismatch of the protein. The strength and range of forces arising from this effect are significantly larger than those that could arise from membrane elasticity for the membranes considered. DOI: http://dx.doi.org/10.7554/eLife.13150.001 The membrane that surrounds cells provides a selective barrier that allows some molecules through, but blocks the path of others. A cell’s membrane is made up of two layers of molecules with oily tails, and is therefore known as a bilayer. Many proteins are dotted within and on the inner and outer surfaces of the bilayer: some act as channels that control what goes in and out of the cell, while others protrude outside the cell so that they can sense changes in the environment. Membrane proteins can move and interact within the bilayer, and various models have emerged to try to explain this dynamic system. These models are based on the membrane having some fluidity but also having regions where there is more structure, and typically describe the proteins as ordered clusters floating in an otherwise disordered fluid membrane. However, many researchers now think some proteins that pass through both layers of the bilayer (i.e., transmembrane proteins) make membranes more ordered, with a possibly gel-like state. However, it is not clear how transmembrane proteins can move and assemble together within such a relatively rigid membrane. To investigate this, Katira, Mandadapu, Vaikuntanathan et al. carried out computer simulations using a model of a simple bilayer membrane. This membrane can exist in an ordered state, where the oily tails are neatly aligned, or a disordered state, where they are irregularly packed. Virtual ‘heating’ of the membrane caused it to shift from an ordered to a disordered state. When a simple transmembrane protein favoring the disordered state was inserted into the ordered state of the modeled membrane, disordered regions formed locally around the protein and the protein was able to diffuse within the membrane. Modeling what would happen if two transmembrane proteins approached each other revealed that a consequence of the order–disorder transition is a strong attractive force that assembles the proteins together. Katira, Mandadapu, Vaikuntanathan et al. named this new phenomenon the 'orderphobic effect'. The forces arising from this effect were much greater than those currently believed to contribute to the assembly of membrane protein complexes, such as those generated by the elasticity of the membrane. This means that the orderphobic effect may be responsible for generating the protein clusters commonly seen in cell membranes. Future work should next explore the opposite effect, where proteins favoring the ordered state are inserted into the disordered state of a membrane. This is expected to cause clustering of such proteins and thus large ordered regions in an otherwise disordered membrane. DOI: http://dx.doi.org/10.7554/eLife.13150.002