Pressure and Osmolyte Effects on Liquid-Liquid Phase Separation Phenomena and Condensates of Proteins

压力和渗透剂对液-液相分离现象和蛋白质凝聚物的影响

• 批准号: 429188951
• 负责人: Professor Dr. Roland Winter
• 金额: --
• 依托单位: Lehrstuhl für Physikalische Chemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/429188951?language=en
• 关键词: Pressure; Osmolyte; Effects; Liquid; Phase

In recent years, liquid-liquid phase separation (LLPS) phenomena have been recognized to play an important role in the membrane-less compartmentalization of cells through the formation of biomolecular condensates. Using UV/Vis, CD, FTIR spectroscopies, phase-contrast light and fluorescence microscopy techniques, we plan to study the combined effects of temperature, pressure and natural osmolytes on LLPS phenomena of different types of such condensates, focusing essentially on the effect of pressure up to the kbar-regime. First studies of our group have shown, quite unexpectedly, that liquid-liquid phase transitions of proteins are among the most pressure sensitive processes found in Nature. Hence, organisms thriving at high-pressure conditions in the deep sea, where pressures up to 1 kbar regime are encountered, have to cope with this high pressure-sensitivity of biomolecular condensates, probably utilizing particular osmolytes. We will then scrutinize the effectiveness of such membrane-less compartments under extreme environmental conditions in modulating the partitioning, conformational dynamics, self-assembly, and activity of peptides and nucleic acids. As life probably started in the deep sea, this knowledge will also shed light on the possible evolutionary advantages of utilizing LLPS for biological function and provide insights into the self-organization principles underpinning cellular evolution in the face of external stresses.

近年来，液-液相分离（LLPS）现象已被认识到通过形成生物分子凝聚物在细胞的无膜区室化中起重要作用。使用UV/维斯，CD，FTIR光谱，相差光和荧光显微镜技术，我们计划研究的综合效应的温度，压力和天然渗透剂对LLPS现象的不同类型的这种冷凝物，主要集中在压力的影响到kbar制度。我们小组的第一项研究非常意外地表明，蛋白质的液-液相变是自然界中发现的最具压力敏感性的过程之一。因此，在深海高压条件下生长的生物体，在那里遇到的压力高达1千巴，必须科普生物分子凝聚物的这种高压力敏感性，可能利用特定的渗透剂。然后，我们将仔细研究这种无膜隔室在极端环境条件下调节肽和核酸的分配，构象动力学，自组装和活性的有效性。由于生命可能起源于深海，这一知识也将揭示利用LLPS进行生物功能的可能进化优势，并提供对支撑细胞进化的自组织原则的见解。