Mutation of exposed hydrophobic amino acids to arginine to increase protein stability
Caroline Strub, Carole Alie, Andrée Lougarre, Caroline Ladurantie, Jerzy Czaplicki and Didier Fournier
Institut de Pharmacologie et de Biologie Structurale, 205 Route de Narbonne, 31077 Toulouse, France
One strategy to increase the stability of proteins is to reduce the area of water-accessible hydrophobic surface.
In order to test it, we replaced 14 solvent-exposed hydrophobic residues of acetylcholinesterase by arginine. The stabilities of the resulting proteins were tested using denaturation by high temperature, organic solvents, urea and by proteolytic digestion.
Altough the mutational effects were rather small, this strategy proved to be successful since half of the mutants showed an increased stability. This stability may originate from the suppression of unfavorable interactions of nonpolar residues with water or from addition of new hydrogen bonds with the solvent. Other mechanisms may also contribute to the increased stability observed with some mutants. For example, introduction of a charge at the surface of the protein may provide a new coulombic interaction on the protein surface.
Source: BMC Biochemistry 2004, 5:9. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.