The ability of salts to stabilize proteins in vivo or intracellularly correlates with the Hofmeister series of ions

Numerous studies have been conducted on the ability of salts to stabilize proteins in vitro using purified proteins demonstrating the fact that the ability of salts to stabilize proteins correlates with the Hofmeister series of ions. Using the well characterized bacterial aqueous cytosolic β-galactosidase and catechol 2,3-dioxygenase enzymes, we demonstrated that salts can stabilize proteins in vivo or intracellularly as well and that the ability of salts to stabilize these two proteins intracellularly also correlates with the Hofmeister series of ions. Na₂SO₄ and Na₂HPO₄ were very effective at stabilizing both proteins, followed by NaCl, NH₄Cl and (NH₄)₂HPO₄, while NH₄CH₃CO₂, (NH₄)₂SO₄ and NaCH₃CO₂ did not stabilize either of the proteins. We also investigated the ability of salts to rescue a collection of well characterized nonfunctional β-galactosidase and catechol 2,3-dioxygenase missense mutants that our laboratory has created. 73.33% of the β-galactosidase missense mutants could be rescued by salt, while only 33.33% of the catechol 2,3 dioxygenase missense mutants could be rescued by salt. This observation was explained by the differences in densities for the two proteins. Catechol 2,3 dioxygenase is almost twice as dense or compact as β-galactosidase and thus it is far easier for salts to penetrate and rescue inactive β-galactosidase proteins. 68.42% of the missense mutants that were rescuable by salt contained mutations that affected amino acids on the surface of the protein and is consistent with the likelihood that salt is able to rescue missense mutants that affect amino acids located on the surface of the protein much more readily than salt can rescue missense mutants that affect amino acids buried in the protein.