Open AccessAn experimental survey of the transition between two-state and downhill protein folding scenarios
Author(s) -
Feng Li,
Deguo Du,
Amelia A. Fuller,
Jennifer E. Davoren,
Peter Wipf,
Jeffery W. Kelly,
Martin Gruebele
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0711908105
Subject(s) - downhill folding , folding (dsp implementation) , protein folding , denaturation (fissile materials) , chemistry , contact order , thermodynamics , melting temperature , biophysics , phi value analysis , ww domain , chemical physics , crystallography , materials science , physics , biology , biochemistry , composite material , gene , electrical engineering , nuclear chemistry , engineering
A kinetic and thermodynamic survey of 35 WW domain sequences is used in combination with a model to discern the energetic requirements for the transition from two-state folding to downhill folding. The sequences used exhibit a 600-fold range of folding rates at the temperature of maximum folding rate. Very stable proteins can achieve complete downhill folding when the temperature is lowered sufficiently below the melting temperature, and then at even lower temperatures they become two-state folders again because of cold denaturation. Less stable proteins never achieve a sufficient bias to fold downhill because of the onset of cold denaturation. The model, considering both heat and cold denaturation, reveals that to achieve incipient downhill folding (barrier <3 RT) or downhill folding (no barrier), the WW domain average melting temperatures have to be >/=50 degrees C for incipient downhill folding and >/=90 degrees C for downhill folding.