A pH Switch for β-Sheet Protein Folding.

ABSTRACT: Protein design advancements have led to biotechnological strategies based on more stable and more specific structures. Herein we present a 6-residue sequence (HPATGK) that acts as a stable structure-nucleating turn at physiological and higher pH but is notably unfavorable for chain direction reversal at low pH. When placed into the turn of a β-sheet, this leads to a pH switch of folding. Using a standard 3-stranded β-sheet model, the WW domain, it was found that the pH switch sequence insertion caused minimal change at pH 8 but a ca. 50 °C drop in the melting temperature (T_m ) was observed at pH 2.5: ΔΔG_F ≥11.3 kJ mol^-1 . Using the strategies demonstrated in this article, the redesign of β-sheets to contain a global, or local, pH-dependent conformational sw

SUBMITTER: Anderson JM 

PROVIDER: S-EPMC5607017 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature