Evolutionary conservation in protein folding kinetics.
The sequence and structural conservation of folding transition states have been predicted on theoretical grounds. Using homologous sequence alignments of proteins previously characterized via coupled mutagenesis/kinetics studies, we tested these predictions experimentally. Only one of the six appropriately characterized proteins exhibits a statistically significant correlation between residues' roles in transition state structure and their evolutionary conservation. However, a significant correlation is observed between the contributions of individual sequence positions to the transition state structure across a set of homologous proteins. Thus the structure of the folding transition state ensemble appears to be more highly conserved than the specific interactions that stabilize it.
Plaxco
K W
KW
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. kwplaxco@u.washington.edu
Larson
S
S
Ruczinski
I
I
Riddle
D S
DS
Thayer
E C
EC
Buchwitz
B
B
Davidson
A R
AR
Baker
D
D
D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D007700:Kinetics; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013223:Statistics as Topic; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D018909:src Homology Domains
D011506:Proteins