title: Evolutionary conservation in protein folding kinetics.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. kwplaxco@u.washington.edu
authors.forename: K W
authors.initials: KW
authors.lastname: Plaxco
authors.forename: S
authors.initials: S
authors.lastname: Larson
authors.forename: I
authors.initials: I
authors.lastname: Ruczinski
authors.forename: D S
authors.initials: DS
authors.lastname: Riddle
authors.forename: E C
authors.initials: EC
authors.lastname: Thayer
authors.forename: B
authors.initials: B
authors.lastname: Buchwitz
authors.forename: A R
authors.initials: AR
authors.lastname: Davidson
authors.forename: D
authors.initials: D
authors.lastname: Baker
mesh_terms: 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
chemical_list: D011506:Proteins