Strategic Use of Non-Native Diselenide Bridges to Steer Oxidative Protein Folding

摘要

Oxidation of cysteine thiols to disulfides is a widespread posttranslational modification of exported proteins, including many of pharmaceutical interest. For disulfide-rich proteins, many different disulfide-bonded species are possible, and the pathway from a reduced unfolded polypeptide chain to the fully oxidized, native conformation may entail multiple oxidation, reduction, and rearrangement steps. Not surprisingly, formation of scrambled disulfide isomers or accumulation of kinetically and conformationally trapped intermediates often limits the rates and yields of oxidative protein folding. Biotechnological production of such proteins would consequently benefit from strategies that improve folding efficiency.