Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding
Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding
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熵力驱动 A M2 型流感病毒萌芽期间的聚类和空间定位
DOI：
10.1101/291120
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Madsen J
中科院分区：
文献类型：
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作者：
Madsen J
甲型流感病毒基质2（M2）跨膜蛋白促进病毒体从感染的宿主细胞释放。特别是，M2在诱导膜弯曲和/或在裂解过程中起作用，由此包膜在病毒体释放时被切割。在这里，我们使用粗粒度的计算机模拟，各种M2组装几何形状出现由于熵驱动力，导致紧凑的集群或线性扩展的聚集体作为一个直接后果的横向膜应力。条件下，这些蛋白质组装将导致脂质膜弯曲的探索，我们预测，一个关键的集群大小是需要这种情况发生。我们继续证明，在细胞膜中发生的应力条件下，因为它经历了大规模的膜重塑，原则上，M2蛋白将能够有助于曲率诱导和感知曲率，以在局部膜线张力高的歧管中排队。发现M2在液体无序液体有序相分离的脂质混合物中表现出linactant行为，并被排除在液体有序相之外，与实验观察接近定量一致。我们的研究结果支持M2在流感病毒出芽过程中作为诱导剂和膜曲率传感器的膜重塑中的作用，并且他们提出了一种机制，通过该机制，M2的定位可以随着病毒体组装和从宿主细胞释放而发生，而不依赖于膜曲率是如何产生的。
The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered–liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.