Preorganized secondary structure as an important determinant of fast protein folding.
The folding and unfolding kinetics of the B-domain of staphylococcal protein A, a small three-helix bundle protein, were probed by NMR. The lineshape of a single histidine resonance was fit as a function of denaturant to give folding and unfolding rate constants. The B-domain folds extremely rapidly in a two-state manner, with a folding rate constant of 120,000 s-1, making it one of the fastest-folding proteins known. Diffusion-collision theory predicts folding and unfolding rate constants that are in good agreement with the experimental values. The apparent rate constant as a function of denaturant ('chevron plot') is predicted within an order of magnitude. Our results are consistent with a model whereby fast-folding proteins utilize a diffusion-collision mechanism, with the preorganization of one or more elements of secondary structure in the unfolded protein.
Myers
J K
JK
Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, North Carolina 27710, USA.
Oas
T G
TG
D002942:Circular Dichroism; D004058:Diffusion; D019791:Guanidine / Q000494:pharmacology; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013205:Staphylococcal Protein A / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D013205:Staphylococcal Protein A; D011392:Proline; D019791:Guanidine