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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 international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201700860
Subject(s) - chemistry , folding (dsp implementation) , beta sheet , turn (biochemistry) , sequence (biology) , protein folding , polypeptide chain , biophysics , crystallography , conformational change , protein structure , stereochemistry , biochemistry , amino acid , electrical engineering , biology , engineering
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.