{"title":"Amino Acids and Their Biological Derivatives Modulate Protein–Protein Interactions in an Additive Way","authors":"Xufeng Xu*, and , Francesco Stellacci*, ","doi":"10.1021/acs.jpclett.4c01175","DOIUrl":null,"url":null,"abstract":"<p >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.</p>","PeriodicalId":62,"journal":{"name":"The Journal of Physical Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jpclett.4c01175","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Physical Chemistry Letters","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jpclett.4c01175","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
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蛋白质与蛋白质之间的相互作用(PPIs)会有所不同。游离氨基酸(AA)及其衍生物占细胞内体积和质量的很大一部分。最近,我们发现 AAs 具有一种通用特性,即通过减少 PPIs 的净吸引部分而使蛋白质分散更加稳定。在此,我们研究了不同 AA 衍生物、AA 混合物和短肽对 PPI 的影响。我们发现,所有测试过的 AA 衍生物都能像 AA 一样有效地调节溶液中的 PPI。此外,我们还发现当 AA 形成混合物或与短肽结合时,其调节作用是相加的。因此,本研究证明了一类小分子(即 AAs 及其生物衍生物)对 PPIs 的叠加效应,并为合理设计生物相容性分子以稳定蛋白质相互作用并进而调整蛋白质功能提供了启示。
期刊介绍:
The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.