芳香族氨基酸组成对肽段液-液相分离的调控
Regulation of Peptide Liquid-Liquid Phase Separation by Aromatic Amino Acid Composition.
作者信息
Netzer Amit, Baruch Leshem Avigail, Veretnik Shirel, Edelstein Ilan, Lampel Ayala
机构信息
Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, 69978, Israel.
出版信息
Small. 2024 Sep;20(38):e2401665. doi: 10.1002/smll.202401665. Epub 2024 May 28.
Membraneless organelles are cellular biomolecular condensates that are formed by liquid-liquid phase separation (LLPS) of proteins and nucleic acids. LLPS is driven by multiple weak attractive forces, including intermolecular interactions mediated by aromatic amino acids. Considering the contribution of π-electron bearing side chains to protein-RNA LLPS, systematically study sought to how the composition of aromatic amino acids affects the formation of heterotypic condensates and their physical properties. For this, a library of minimalistic peptide building blocks is designed containing varying number and compositions of aromatic amino acids. It is shown that the number of aromatics in the peptide sequence affect LLPS propensity, material properties and (bio)chemical stability of peptide/RNA heterotypic condensates. The findings shed light on the contribution of aromatics' composition to the formation of heterotypic condensates. These insights can be applied for regulation of condensate material properties and improvement of their (bio)chemical stability, for various biomedical and biotechnological applications.
无膜细胞器是由蛋白质和核酸的液-液相分离(LLPS)形成的细胞生物分子凝聚物。LLPS由多种弱吸引力驱动,包括由芳香族氨基酸介导的分子间相互作用。考虑到含π电子的侧链对蛋白质-RNA LLPS的贡献,系统研究旨在探究芳香族氨基酸的组成如何影响异型凝聚物的形成及其物理性质。为此,设计了一个简约肽构建模块库,其中包含不同数量和组成的芳香族氨基酸。结果表明,肽序列中芳香族氨基酸的数量会影响肽/RNA异型凝聚物的LLPS倾向、材料性质和(生物)化学稳定性。这些发现揭示了芳香族氨基酸组成对异型凝聚物形成的贡献。这些见解可应用于调节凝聚物材料性质并提高其(生物)化学稳定性,以用于各种生物医学和生物技术应用。