Tuning the free-energy landscape of a WW domain by temperature, mutation, and truncation

Houbi Nguyen, Marcus Jäger, Alessandro Moretto, Martin Gruebele, Jeffery W. Kelly

Research output: Contribution to journalArticlepeer-review


The equilibrium unfolding of the Formin binding protein 28 (FBP) WW domain, a stable three-stranded β-sheet protein, can be described as reversible apparent two-state folding. Kinetics studied by laser temperature jump reveal a third state at temperatures below the midpoint of unfolding. The FBP free-energy surface can be tuned between three-state and two-state kinetics by changing the temperature, by truncation of the C terminus, or by selected point mutations. FBP WW domain is the smallest three-state folder studied to date and the only one that can be freely tuned between three-state and apparent two-state folding by several methods (temperature, truncation, and mutation). Its small size (28-37 residues), the availability of a quantitative reaction coordinate (φT), the fast folding time scale (10s of μs), and the tunability of the folding routes by small temperature or sequence changes make this system the ideal prototype for studying more subtle features of the folding free-energy landscape by simulations or analytical theory.

Original languageEnglish (US)
Pages (from-to)3948-3953
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Apr 1 2003


  • Protien folding mechanism
  • β-sheet
  • β-strand

ASJC Scopus subject areas

  • General


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