Charge-charge interactions in the denatured state influence the folding kinetics of ribonuclease Sa.
Gaining a better understanding of the denatured state ensemble of proteins is important for understanding protein stability and the mechanism of protein folding. We studied the folding kinetics of ribonuclease Sa (RNase Sa) and a charge-reversal variant (D17R). The refolding kinetics are similar, but the unfolding rate constant is 10-fold greater for the variant. This suggests that charge-charge interactions in the denatured state and the transition state ensembles are more favorable in the variant than in RNase Sa, and shows that charge-charge interactions can influence the kinetics and mechanism of protein folding.
Trefethen
Jared M
JM
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-1114, USA.
Pace
C Nick
CN
Scholtz
J Martin
JM
Brems
David N
DN
D004795:Enzyme Stability; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics; D007700:Kinetics; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D012260:Ribonucleases / Q000737:chemistry* / Q000235:genetics
D007527:Isoenzymes; D012260:Ribonucleases; C077002:ribonuclease Sa3