Smokers Iris B A, Lavagna Enrico, Freire Rafael V M, Paloni Matteo, Voets Ilja K, Barducci Alessandro, White Paul B, Khajehpour Mazdak, Spruijt Evan
Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Centre de Biologie Structurale, Université de Montpellier, CNRS, INSERM, Montpellier 34090, France.
J Am Chem Soc. 2025 Jul 23;147(29):25692-25704. doi: 10.1021/jacs.5c07295. Epub 2025 Jul 13.
Biomolecular condensates modulate various ion-dependent cellular processes and can regulate subcellular ion distributions by selective uptake of ions. To understand these processes, it is essential to uncover the molecular grammar governing condensate-ion interactions. Here, we use nuclear magnetic resonance (NMR) spectroscopy of ions and model condensate components to quantify and spatially resolve selective ion binding to condensates and show that these interactions follow the "law of matching water affinities", resulting in strong binding between proteins and chaotropic anions and between nucleic acids and kosmotropic cations. Ion uptake into condensates directly follows binding affinities, resulting in selective uptake of strong-binding ions but exclusion of weak-binding ions. Ion binding further shapes the condensate microenvironment by altering the composition, viscosity, and interface potential. Such changes can have profound effects on biochemical processes taking place inside condensates, as we show for RNA duplex formation. Our findings provide a new perspective on the role of condensate-ion interactions in cellular bio- and electrochemistry and may aid the design of condensate-targeting therapeutics.
生物分子凝聚物调节各种离子依赖的细胞过程，并可通过选择性摄取离子来调节亚细胞离子分布。为了解这些过程，揭示支配凝聚物 - 离子相互作用的分子规则至关重要。在此，我们利用离子和模型凝聚物成分的核磁共振（NMR）光谱来量化并在空间上解析选择性离子与凝聚物的结合，结果表明这些相互作用遵循“水亲和力匹配定律”，导致蛋白质与离液序列高的阴离子之间以及核酸与促溶阳离子之间存在强结合。离子进入凝聚物直接遵循结合亲和力，导致选择性摄取强结合离子但排斥弱结合离子。离子结合通过改变组成、粘度和界面电位进一步塑造凝聚物微环境。正如我们在RNA双链体形成中所展示的那样，这种变化会对凝聚物内部发生的生化过程产生深远影响。我们的研究结果为凝聚物 - 离子相互作用在细胞生物化学和电化学中的作用提供了新视角，并可能有助于设计靶向凝聚物的疗法。
