Allosteric disulfide bonds

Abstract

Protein disulfide bonds link cysteine residues in the polypeptide chain. The bonds contribute, sometimes crucially, to protein stability and function and are strongly conserved through the evolution of species. By analyzing the conservation of all structurally validated disulfide bonds across 29 completely sequenced eukaryotic genomes, we found that disulfide-bonded cysteines are even more conserved than tryptophan - the most conserved amino acid. Moreover, the rate of acquisition of disulfide bonds shows a strong positive correlation with organism complexity, which probably reflects the requirement for more sophistication in protein function in complex species. The majority of disulfide bonds perform a structural role by stabilizing the mature protein. Some disulfide bonds perform a functional role in the mature protein and can be divided into catalytic or allosteric disulfides. Catalytic disulfides/dithiols transfer electrons between proteins, while the allosteric bonds control the function of the protein in which they reside when they break and/or form. There are currently a dozen or so examples of allosteric disulfide bonds. The features of these bonds and their involvement in the respective proteins' function are discussed. A common aspect of 11 of the 12 allosteric bonds discussed herein is that they link β-strands or β-loops. © 2011 Springer Science+Business Media, LLC.