Removal of surface charge-charge interactions from ubiquitin leaves the protein folded and very stable

The contribution of solvent-exposed charged residues to protein stability was evaluated using ubiquitin as a model protein.We combined site-directed mutagenesis and specific chemical modifications to first replace all Arg residues with Lys, followed by carbomylation of Lys-amino groups.Under the conditions in which all carboxylic groups are protonated (at pH 2), the chemically modified protein is folded and very stable (⌬G ‫ס‬ 18 kJ/mol).These results indicate that surface charge-charge interactions are not an essential fundamental force for protein folding and stability.