Mapping the transition state of the WW domain β-sheet

Jason C. Crane, Edward K. Koepf, Jeffery W. Kelly, Martin Gruebele

Research output: Contribution to journalArticlepeer-review


The folding kinetics of a three-stranded antiparallel β-sheet (WW domain) have been measured by temperature jump relaxation. Folding and activation free energies were determined as a function of temperature for both the wild-type and the mutant domain, W39F, which modifies the β23 hydrophobic interface. The folding rate decreases at higher temperatures as a result of the increase in the activation free energy for folding. Φ-Values were obtained for thermal perturbations allowing the primary features of the folding free energy surface to be determined. The results of this analysis indicate a significant shift from an 'early' (Φ(T) = 0.4) to a 'late' (Φ(T) = 0.8) transition state with increasing temperature. The temperature-dependent Φ-value analysis of the wild-type WW domain and of its more stable W39F hydrophobic cluster mutant reveals little participation of residue 39 in the transition state at lower temperature. As the temperature is raised, hydrophobic interactions at the β23 interface gain importance in the transition state and the barrier height of the wild-type, which contains the larger tryptophan residue, increases more slowly than the barrier height of the mutant. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)283-292
Number of pages10
JournalJournal of Molecular Biology
Issue number2
StatePublished - Apr 28 2000


  • Hydrophobic effect
  • Kramers theory
  • Phi-value
  • Protein folding
  • β-Hairpin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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