The intracellular environment affects protein–protein interactions

Significance Protein–protein interactions are essential for proper cellular function. Macromolecular crowding can influence these interactions via two phenomena: hard-core repulsions and soft (chemical) interactions. Simple theory predicts that hard-core repulsions are stabilizing, and stabilization increases with increased crowding, while chemical interactions can be stabilizing or destabilizing. We investigated the effect of the cellular environment on a model protein–protein interaction in a prokaryote ( Escherichia coli ) and a eukaryote ( Xenopus laevis oocytes). The observation that the complex is more stable in the eukaryote, even though it is less crowded, highlights the key role played by chemical interactions under physiologically relevant conditions.