TY - JOUR
T1 - Eliminating a Protein Folding Intermediate by Tuning a Local Hydrophobic Contact
AU - Kachlishvili, Khatuna
AU - Dave, Kapil
AU - Gruebele, Martin
AU - Scheraga, Harold A.
AU - Maisuradze, Gia G.
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2017/4/20
Y1 - 2017/4/20
N2 - Intermediate states in protein folding may slow folding, and sometimes can provide a starting point for aggregation. Recently, the FBP28 WW domain of the formin-binding protein was used as a model for a computational study of the origin and prevention of intermediate-state formation, and local hydrophobic interactions of Leu26 were implicated. Here, we combine new simulations over a broad temperature range with experimental temperature-jump data to study this site in more detail. We replace Leu26 by Asp26 or Trp26 to alter the folding scenario from three-state folding toward two-state or downhill folding at temperatures below the melting point, whereas the wild type shows two-state behavior only near its melting temperature. We offer an explanation of this behavior mainly in terms of principles of hydrophobic interactions.
AB - Intermediate states in protein folding may slow folding, and sometimes can provide a starting point for aggregation. Recently, the FBP28 WW domain of the formin-binding protein was used as a model for a computational study of the origin and prevention of intermediate-state formation, and local hydrophobic interactions of Leu26 were implicated. Here, we combine new simulations over a broad temperature range with experimental temperature-jump data to study this site in more detail. We replace Leu26 by Asp26 or Trp26 to alter the folding scenario from three-state folding toward two-state or downhill folding at temperatures below the melting point, whereas the wild type shows two-state behavior only near its melting temperature. We offer an explanation of this behavior mainly in terms of principles of hydrophobic interactions.
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U2 - 10.1021/acs.jpcb.6b07250
DO - 10.1021/acs.jpcb.6b07250
M3 - Article
C2 - 27584585
AN - SCOPUS:85020042781
SN - 1520-6106
VL - 121
SP - 3276
EP - 3284
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 15
ER -