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A pH Switch for ?-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 ?-sheet, this leads to a pH switch of folding. Using a standard 3-stranded ?-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 (Tm ) was observed at pH?2.5: ??GF ?11.3?kJ?mol-1 . Using the strategies demonstrated in this article, the redesign of ?-sheets to contain a global, or local, pH-dependent conformational switch should be possible.

SUBMITTER: Anderson JM

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

REPOSITORIES: biostudies-literature

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A pH Switch for β-Sheet Protein Folding.

Anderson Jordan M JM Andersen Niels H NH

Angewandte Chemie (International ed. in English) 20170519 25

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 ...[more]

PMID: 28523654

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