Li Zhenlong, Gorfe Alemayehu A
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Small GTPases. 2012 Oct-Dec;3(4):244-7. doi: 10.4161/sgtp.21829. Epub 2012 Aug 30.
The dynamic assembly and lateral organization of Ras proteins on the plasma membrane has been the focus of much research in recent years. It has been shown that different isoforms of Ras proteins share a nearly identical catalytic domain, yet form distinct and non-overlapping nanoclusters. Though this difference in the clustering behavior of Ras proteins has been attributed largely to their different C terminal lipid modification, its precise physical basis was not determined. Recently, we used computer simulations to study the mechanism by which the triply lipid-modified membrane-anchor of H-ras, and its partially de-lipidated variants, form nanoclusters in a model lipid bilayer. We found that the specific nature of the lipid modification is less important for cluster formation, but plays a key role for the domain-specific distribution of the nanoclusters. Here we provide additional details on the interplay between bilayer structure perturbation and peptide-peptide association that provide the physical driving force for clustering. We present some thoughts about how enthalpic (i.e., interaction) and entropic effects might regulate nanocluster size and stability.
近年来，Ras蛋白在质膜上的动态组装和侧向组织一直是众多研究的焦点。研究表明，Ras蛋白的不同异构体共享几乎相同的催化结构域，但形成了不同且不重叠的纳米簇。尽管Ras蛋白聚集行为的这种差异在很大程度上归因于它们不同的C末端脂质修饰，但其精确的物理基础尚未确定。最近，我们使用计算机模拟来研究H-ras的三重脂质修饰膜锚及其部分去脂变体在模型脂质双层中形成纳米簇的机制。我们发现，脂质修饰的具体性质对簇形成的重要性较低，但对纳米簇的结构域特异性分布起着关键作用。在此，我们提供了关于双层结构扰动与肽-肽缔合之间相互作用的更多细节，这种相互作用为聚集提供了物理驱动力。我们提出了一些关于焓（即相互作用）和熵效应如何调节纳米簇大小和稳定性的想法。
