Robustness of protein folding kinetics to surface hydrophobic substitutions.
We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.
Gu
H
H
Department of Biochemistry, University of Washington, Seattle 98195, USA.
Doshi
N
N
Kim
D E
DE
Simons
K T
KT
Santiago
J V
JV
Nauli
S
S
Baker
D
D
D019943:Amino Acid Substitution; D001426:Bacterial Proteins; D020650:Combinatorial Chemistry Techniques; D004268:DNA-Binding Proteins / Q000737:chemistry*; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D010462:Peptostreptococcus / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D018909:src Homology Domains
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C116593:L-protein, Peptococcus magnus