Protein–protein interactions are fundamental to biology yet are rarely studied under physiologically relevant conditions where the concentration of macromolecules can exceed 300 g/L. These high concentrations cause cosolute–complex contacts that are absent in dilute buffer. Understanding such interactions is important because they organize the cellular interior. We used ¹⁹F nuclear magnetic resonance, the dimer-forming A34F variant of the model protein GB1, and the cosolutes bovine serum albumin (BSA) and lysozyme to assess the effects of repulsive and attractive charge–charge dimer–cosolute interactions on dimer stability. The interactions were also manipulated via charge-change variants and by changing the pH. Charge–charge repulsions between BSA and GB1 stabilize the dimer, and the effects of lysozyme indicate a role for attractive interactions. The data show that chemical interactions can regulate the strength of protein–protein interactions under physiologically relevant crowded conditions and suggest a mechanism for tuning the equilibrium thermodynamics of protein–protein interactions in cells.

中文翻译：

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在生理相关环境中，表面电荷调节蛋白质与蛋白质的相互作用

蛋白质间的相互作用是生物学的基础，但在生理上相关的条件下（大分子浓度可以超过300 g / L）很少进行研究。这些高浓度导致稀缓冲液中不存在的固溶-复杂接触。了解此类交互非常重要，因为它们会组织细胞内部。我们用了¹⁹F核磁共振，模型蛋白GB1的形成二聚体的A34F变体以及牛血清白蛋白（BSA）和溶菌酶的固溶体，以评估排斥性和有吸引力的电荷-电荷二聚体-固溶体相互作用对二聚体稳定性的影响。还通过电荷变化变体和pH值来控制相互作用。BSA和GB1之间的电荷-电荷排斥作用稳定了二聚体，溶菌酶的作用表明了有吸引力的相互作用。数据表明，在生理相关的拥挤条件下，化学相互作用可以调节蛋白质-蛋白质相互作用的强度，并提出了调节细胞中蛋白质-蛋白质相互作用的平衡热力学的机制。