Evidence for a molten globule-like transition state in protein folding from determination of activation volumes.
One of the most important, yet elusive, aspects of the protein folding question lies in the nature of the transition state. Direct information about the structural properties of the transition state can be obtained from determination of the activation volumes for the folding and unfolding transitions. The present pressure-jump relaxation study on the folding/unfolding of staphylococcal nuclease reveals that the volume of the protein-solvent system is larger in the transition state than in either the folded or unfolded states. Moreover, the activation volume of folding is much larger than that of unfolding. These results support a molten globule-like model for the transition state of nuclease in which the polypeptide chain is in a collapsed, loosely packed, solvent-excluded structure. In this model, hydrophobic collapse with concomitant desolvation is the rate-limiting step in the folding of the polypeptide chain, and solvent-excluded expansion of the folded state is the rate-limiting step in protein unfolding.
Vidugiris
G J
GJ
School of Pharmacy, University of Wisconsin-Madison 53706, USA.
Markley
J L
JL
Royer
C A
CA
D007700:Kinetics; D008836:Micrococcal Nuclease / Q000737:chemistry; D008956:Models, Chemical; D011312:Pressure; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry; D013816:Thermodynamics
D011994:Recombinant Proteins; D008836:Micrococcal Nuclease