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The role of the turn in β‐hairpin formation during WW domain folding
Author(s) -
Sharpe Tim,
Jonsson Amanda L.,
Rutherford Trevor J.,
Daggett Valerie,
Fersht Alan R.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.073004907
Subject(s) - ww domain , folding (dsp implementation) , turn (biochemistry) , protein folding , nucleation , chemistry , molecular dynamics , crystallography , energetics , biophysics , nucleus , chemical physics , phi value analysis , downhill folding , physics , computational chemistry , thermodynamics , biology , biochemistry , organic chemistry , microbiology and biotechnology , electrical engineering , gene , engineering
The folding of WW domains is rate limited by formation of a β‐hairpin comprising residues from strands 1 and 2. Residues in the turn of this hairpin have reported Φ‐values for folding close to 1 and have been proposed to nucleate folding. High Φ‐values do not necessarily imply that the energetics of formation are a driving force for initiating folding. We demonstrate by NMR studies and molecular dynamics simulations that the first turn of the hYAP, FBP28, and PIN1 WW domains is structurally dynamic and solvent exposed in the native and folding transition states. It is, therefore, unlikely that the formation of the β‐turn per se provides the energetic driving force for hairpin folding. It is more likely that the turn acts as an easily formed hinge that facilitates the formation of the hairpin; it is a nucleus as defined by the nucleation–condensation mechanism whereby a diffuse nucleus is stabilized by associated interactions.