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Surface Charge Modulates Protein–Protein Interactions in Physiologically Relevant Environments

Guseman, Alex J., Speer, Shannon L., Perez Goncalves, Gerardo M., Pielak, Gary J.
Biochemistry 2018 v.57 no.11 pp. 1681-1684
bovine serum albumin, lysozyme, models, nuclear magnetic resonance spectroscopy, pH, protein-protein interactions, solutes, thermodynamics
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.