Theory for protein folding cooperativity: helix bundles.
We present a theory for protein folding stability and cooperativity for helix bundle proteins. We treat the individual helices with a Schellman-Zimm-Bragg-like approach, using nucleation and propagation quantities, and we treat the hydrophobic and van der Waals contacts between the helices as a binding equilibrium. Predictions are in good agreement with experiments on both thermal and urea-induced transitions of (1) molecules that can undergo single helix-to-coil transitions for various chain lengths and (2) three-helix-bundle proteins A and alpha3C. The present model addresses a problem raised by Kaya and Chan that proteins fold more cooperatively than previous models predict. The present model correctly predicts the experimentally observed two-state cooperativities, DeltaH(van't Hoff)/DeltaH(cal) approximately 1, for helix-bundle proteins. The predicted folding cooperativity is greater than that of helix formation alone, or collapse alone, because of the nonlinear coupling between the tertiary interactions and the helical interactions.
Ghosh
Kingshuk
K
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Dill
K A
KA
D008956:Models, Chemical; D008958:Models, Molecular; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013205:Staphylococcal Protein A / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins; D013205:Staphylococcal Protein A; C505583:alpha3C protein