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A pH Switch for β‐Sheet Protein Folding
Author(s) -
Anderson Jordan M.,
Andersen Niels H.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201700860
Subject(s) - chemistry , turn (biochemistry) , beta sheet , folding (dsp implementation) , sequence (biology) , protein folding , polypeptide chain , crystallography , melting temperature , biophysics , conformational change , residue (chemistry) , protein structure , stereochemistry , biochemistry , materials science , amino acid , biology , electrical engineering , engineering , composite material
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 switch should be possible.