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PubMed · 10764599

Evolutionary conservation in protein folding kinetics.

K W Plaxco·S Larson·I Ruczinski·D S Riddle·E C Thayer·B Buchwitz·A R Davidson·D Baker
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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.

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AnimalsBinding SitesConserved SequenceEvolution, MolecularKineticsMutationProtein ConformationProtein FoldingProteinsSequence AlignmentSequence Homology, Amino AcidStatistics as TopicStructure-Activity RelationshipThermodynamicssrc Homology DomainsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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K W Plaxco, S Larson, I Ruczinski, D S Riddle, E C Thayer, B Buchwitz, A R Davidson, D Baker. 2000-04-28. Evolutionary conservation in protein folding kinetics.. https://doi.org/10.1006/jmbi.1999.3663

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