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Using D-amino acids to delineate the mechanism of protein folding: Application to Trp-cage

Authors
Journal
Chemical Physics
0301-0104
Publisher
Elsevier
Publication Date
Volume
422
Identifiers
DOI: 10.1016/j.chemphys.2013.01.021
Keywords
  • Protein Folding
  • D-Amino Acid
  • T-Jump
  • Infrared
Disciplines
  • Biology

Abstract

Abstract Using the miniprotein Trp-cage as a model, we show that D-amino acids can be used to facilitate the delineation of protein folding mechanism. Specifically, we study the folding–unfolding kinetics of three Trp-cage mutants where the native glycine residue near the C-terminus of the α-helix is replaced by a D-amino acid. A previous study showed that these mutations increase the Trp-cage stability, due to a terminal capping effect. Our results show that the stabilizing effect of D-asparagine and d-glutamine originates almost exclusively from a decrease in the unfolding rate, while the D-alanine mutation results in a similar decrease in the unfolding rate, but it also increases the folding rate. Together, these results support a folding mechanism wherein the α-helix formation in the transition state is nucleated at the N-terminus, whereas those long-range native interactions stabilizing this helix are developed at the downhill side of the folding free energy barrier.

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