An experimental investigation of conformational fluctuations in proteins G and L.
The B1 domains of streptococcal proteins G and L are structurally similar, but they have different sequences and they fold differently. We have measured their NMR spectra at variable temperature using a range of concentrations of denaturant. Many residues have curved amide proton temperature dependence, indicating that they significantly populate alternative, locally unfolded conformations. The results, therefore, provide a view of the locations of low-lying, locally unfolded conformations. They indicate approximately 4-6 local minima for each protein, all within ca. 2.5 kcal/mol of the native state, implying a locally rough energy landscape. Comparison with folding data for these proteins shows that folding involves most molecules traversing a similar path, once a transition state containing a beta hairpin has been formed, thereby defining a well-populated pathway down the folding funnel. The hairpin that directs the folding pathway differs for the two proteins and remains the most stable part of the folded protein.
Tunnicliffe
Richard B
RB
Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, United Kingdom.
Waby
Joe L
JL
Williams
Ryan J
RJ
Williamson
Mike P
MP
D001426:Bacterial Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D017510:Protein Folding; D013291:Streptococcus / Q000737:chemistry*; D013696:Temperature
D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus