Distinct Features of Stress Granule Proteins Predict Localization in Membraneless Organelles.,Journal of Molecular Biology

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Distinct Features of Stress Granule Proteins Predict Localization in Membraneless Organelles.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.jmb.2020.02.020
Erich R Kuechler ₁ , Paulina M Budzyńska ₁ , Jonathan P Bernardini ₁ , Jörg Gsponer ₁ , Thibault Mayor ₁

Affiliation

Recently generated proteomic data provides unprecedented insight into stress granule composition and stands as fruitful ground for further analysis. Stress granules are stress-induced biological assemblies that are of keen interest due to being linked to both long-term cell viability and a variety of protein aggregation-based diseases. Herein, we compile recently published stress granule composition data, formed specifically through heat and oxidative stress, for both mammalian (Homo sapiens) and yeast (Saccharomyces cerevisiae) cells. Interrogation of the data reveals that stress granule proteins are enriched in features that favor protein liquid-liquid phase separation, being highly disordered, soluble, and abundant while maintaining a high level of protein-protein interactions under basal conditions. Furthermore, these "stress granuleomes" are shown to be enriched for multidomained, RNA-binding proteins with increased potential for post-translational modifications. Findings are consistent with the notion that stress granule formation is driven by protein liquid-liquid phase separation. Furthermore, stress granule proteins appear poised near solubility limits while possessing the ability to dynamically alter their phase behavior in response to external threat. Interestingly, several features, such as protein disorder, are more prominent among stress granule proteins that share homologs between yeast and mammalian systems also found within stress-induced foci. We culminate results from our stress granule analysis into novel predictors for granule incorporation and validate the mammalian predictor's performance against multiple types of membraneless condensates and by colocalization microscopy.

中文翻译：

应力颗粒蛋白的不同特征可预测无膜细胞器中的定位。

最近生成的蛋白质组学数据为应力颗粒的组成提供了前所未有的洞察力，为进一步分析奠定了坚实的基础。应力颗粒是应力诱导的生物集合体，由于与长期细胞生存力和多种基于蛋白质聚集的疾病有关，因此引起人们极大的兴趣。在这里，我们针对哺乳动物（Homo sapiens）和酵母（Saccharomyces cerevisiae）细胞汇编了最近发表的通过热和氧化应激形成的应激颗粒组成数据。对数据的询问显示，应激颗粒蛋白的特征丰富，有利于蛋白液-液相分离，高度无序，可溶和丰富，同时在基础条件下仍保持高水平的蛋白-蛋白相互作用。此外，这些“

更新日期：2020-02-24

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