Quinary structure modulates protein stability in cells

Globular proteins perform many of the chemical reactions required for life. The prevailing model of globular protein structure, which is based on studies in dilute solutions, emphasizes the requirement for a well-packed hydrophobic interior, but minimizes the importance of the exterior, provided it is hydrophilic. We demonstrate that the exterior plays a significant role when a globular protein is studied under physiologically relevant conditions. By changing a surface residue we show that attractive interactions between the protein surface and the cytosol modulate the stability of the protein, even though the change has a negligible effect in dilute solution. Recognizing and quantifying such intracellular interactions will aid in understanding and manipulating the biological role of proteins