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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Free-energy distribution of binary protein - protein binding suggests cross-species interactorne differences
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Free-energy distribution of binary protein - protein binding suggests cross-species interactorne differences

机译:二元蛋白的自由能分布-蛋白结合表明跨物种相互作用因子的差异

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Major advances in large-scale yeast two-hybrid screening have provided a global view of binary protein-protein interactions across species as dissimilar as human, yeast, and bacteria. Remarkably, these analyses have revealed that all species studied have a degree distribution of protein-protein binding that is approximately scale-free (varies as a power law) even though their evolutionary divergence times differ by billions of years. The universal power law shows only the surface of the rich information harbored by these high-throughput data. We develop a detailed mathematical model of the protein-protein interaction network based on association free energy, the biochemical quantity that determines protein-protein interaction strength. This model reproduces the degree distribution of all of the large-scale yeast two-hybrid data sets available and allows us to extract the distribution of free energy, the likelihood that a pair of proteins of a given species will bind. We find that across-species interactomes have significant differences that reflect the strengths of the protein-protein interaction. Our results identify a global evolutionary shift: more evolved organisms have weaker binary protein-protein binding. This result is consistent with the evolution of increased protein unfoldedness and challenges the dogma that only specific protein-protein interactions can be biologically functional.
机译:大规模酵母双杂交筛选的重大进展已提供了人类,酵母和细菌等不同物种间二元蛋白质-蛋白质相互作用的全局视图。值得注意的是,这些分析表明,所有研究物种的蛋白质-蛋白质结合程度分布几乎都是无鳞的(随幂律而变化),即使它们的进化差异时间相差数十亿年。通用幂律仅显示了这些高通量数据所包含的丰富信息的表面。我们基于缔合自由能(决定蛋白质-蛋白质相互作用强度的生化量)开发了蛋白质-蛋白质相互作用网络的详细数学模型。该模型再现了所有可用的大规模酵母双杂交数据集的度分布,并允许我们提取自由能的分布,即给定物种的一对蛋白质结合的可能性。我们发现跨物种的相互作用组具有显着差异,反映出蛋白质-蛋白质相互作用的强度。我们的结果表明了全球进化的转变:更多的进化生物具有较弱的二元蛋白质-蛋白质结合。该结果与蛋白质未折叠增加的进化相一致,并向教条提出挑战,即只有特定的蛋白质-蛋白质相互作用才具有生物学功能。

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