Evolutionary conservation in protein folding kinetics

TitleEvolutionary conservation in protein folding kinetics
Publication TypeJournal Article
Year of Publication2000
AuthorsPlaxco, K. W., Larson S., Ruczinski I., Riddle D. S., Thayer E. C., Buchwitz B., Davidson A. R., & Baker D.
JournalJournal of molecular biology
Volume298
Issue2
Pagination303-12
Date Published2000 Apr 28
ISSN0022-2836
KeywordsAnimals, Binding Sites, Conserved Sequence, Evolution, Molecular, Kinetics, Mutation, Primary Publication, Protein Conformation, Protein Folding, Proteins, Sequence Alignment, Sequence Homology, Amino Acid, src Homology Domains, Statistics as Topic, Structure-Activity Relationship, Thermodynamics
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.

Alternate JournalJ. Mol. Biol.
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