FCCC LOGO Faculty Publications
Zhu Y , Alonso DO , Maki K , Huang CY , Lahr SJ , Daggett V , Roder H , DeGrado WF , Gai F
Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26) :15486-91
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Abstract
Here, we describe the folding/unfolding kinetics of alpha3D, a small designed three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing methods reveal a single-exponential process consistent with a minimal folding time of 3.2 +/- 1.2 micros (at approximately 50 degrees C), indicating that a protein can fold on the 1- to 5-micros time scale. Furthermore, the single-exponential nature of the relaxation indicates that the prefactor for transition state (TS)-folding models is probably >or=1 (micros)-1 for a protein of this size and topology. Molecular dynamics simulations and IR spectroscopy provide a molecular rationale for the rapid, single-exponential folding of this protein. alpha3D shows a significant bias toward local helical structure in the thermally denatured state. The molecular dynamics-simulated TS ensemble is highly heterogeneous and dynamic, allowing access to the TS via multiple pathways.
Notes
0027-8424 Journal Article