Protein folding kinetics exhibit an Arrhenius temperature dependence when corrected for the temperature dependence of protein stability.

The anomalous temperature dependence of protein folding has received considerable attention. Here we show that the temperature dependence of the folding of protein L becomes extremely simple when the effects of temperature on protein stability are corrected for; the logarithm of the folding rate is a linear function of 1/T on constant stability contours in the temperature-denaturant plane. This convincingly demonstrates that the anomalous temperature dependence of folding derives from the temperature dependence of the interactions that stabilize proteins, rather than from the super Arrhenius temperature dependence predicted for the configurational diffusion constant on a rough energy landscape. However, because of the limited temperature range accessible to experiment, the results do not rule out models with higher order temperature dependences. The significance of the slope of the stability-corrected Arrhenius plots is discussed.

[1]  H. Gray,et al.  Cytochrome c folding triggered by electron transfer. , 1996, Chemistry & biology.

[2]  J. Onuchic,et al.  DIFFUSIVE DYNAMICS OF THE REACTION COORDINATE FOR PROTEIN FOLDING FUNNELS , 1996, cond-mat/9601091.

[3]  K. Dill,et al.  From Levinthal to pathways to funnels , 1997, Nature Structural Biology.

[4]  J. Onuchic,et al.  Funnels, pathways, and the energy landscape of protein folding: A synthesis , 1994, Proteins.

[5]  J. Onuchic,et al.  Toward an outline of the topography of a realistic protein-folding funnel. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Onuchic,et al.  Fast-folding experiments and the topography of protein folding energy landscapes. , 1996, Chemistry & biology.

[7]  P. Wolynes,et al.  Intermediates and barrier crossing in a random energy model , 1989 .

[8]  I D Campbell,et al.  A comparison of the folding kinetics and thermodynamics of two homologous fibronectin type III modules. , 1997, Journal of molecular biology.

[9]  D Baker,et al.  Kinetics of folding of the IgG binding domain of peptostreptococcal protein L. , 1997, Biochemistry.

[10]  T. Schindler,et al.  Thermodynamic properties of an extremely rapid protein folding reaction. , 1996, Biochemistry.

[11]  R. L. Baldwin,et al.  Temperature dependence of the hydrophobic interaction in protein folding. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[12]  E I Shakhnovich,et al.  Evolution-like selection of fast-folding model proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Baase,et al.  Low-temperature unfolding of a mutant of phage T4 lysozyme. 2. Kinetic investigations. , 1989, Biochemistry.

[14]  D Baker,et al.  A desolvation barrier to hydrophobic cluster formation may contribute to the rate‐limiting step in protein folding , 1997, Protein science : a publication of the Protein Society.

[15]  R. Sauer,et al.  Barriers to protein folding: formation of buried polar interactions is a slow step in acquisition of structure. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  E. Shakhnovich,et al.  Chain Length Scaling of Protein Folding Time. , 1996, Physical review letters.

[17]  P. Alexander,et al.  Kinetic analysis of folding and unfolding the 56 amino acid IgG-binding domain of streptococcal protein G. , 1992, Biochemistry.

[18]  A. Fersht,et al.  Titration properties and thermodynamics of the transition state for folding: comparison of two-state and multi-state folding pathways. , 1996, Journal of molecular biology.