Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Bioengineering Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
J Phys Chem Lett. 2024 Jul 18;15(28):7154-7160. doi: 10.1021/acs.jpclett.4c01175. Epub 2024 Jul 5.
Protein-protein interactions (PPIs) differ when measured in test tubes and cells due to the complexity of the intracellular environment. Free amino acids (AAs) and their derivatives constitute a significant fraction of the intracellular volume and mass. Recently, we have found that AAs have a generic property of rendering protein dispersions more stable by reducing the net attractive part of PPIs. Here, we study the effects on PPIs of different AA derivatives, AA mixtures, and short peptides. We find that all the tested AA derivatives modulate PPIs in solution as effectively as AAs. Furthermore, we show that the modulation effect is additive when AAs form mixtures or are bound into short peptides. Therefore, this study demonstrates the additive effects of a class of small molecules (i.e., AAs and their biological derivatives) on PPIs and provides insights into rationally designing biocompatible molecules for stabilizing protein interactions and consequently tuning protein functions.
由于细胞内环境的复杂性，在试管和细胞中测量时，蛋白质-蛋白质相互作用（PPIs）会有所不同。游离氨基酸（AAs）及其衍生物构成了细胞内体积和质量的重要部分。最近，我们发现 AAs 具有通过减少 PPIs 的净吸引力部分使蛋白质分散体更稳定的通用性质。在这里，我们研究了不同 AA 衍生物、AA 混合物和短肽对 PPIs 的影响。我们发现所有测试的 AA 衍生物在溶液中都能像 AAs 一样有效地调节 PPIs。此外，我们还表明，当 AAs 形成混合物或结合成短肽时，调节作用是累加的。因此，这项研究证明了一类小分子（即 AAs 和它们的生物衍生物）对 PPIs 的累加效应，并为合理设计稳定蛋白质相互作用的生物相容性分子以及调节蛋白质功能提供了思路。
