| In recent years, several studies on the folding mechanism of the Src and alpha-spectrin SH3 domains have found the folding transition state to be conformationally restricted and evolutionarily conserved. In both the Src and Spectrin SH3, it was found that the folding transition state structure was structurally polarized with the distal loop next to a hydrophobic cluster that is highly ordered in the transition state. In this study, the folding and unfolding kinetics of a large number of mutants at positions in the Fyn SH3 domain, that correspond to positions previously studied in the Src and Spectrin domains, have been examined. The kinetic importance of a buried polar interaction (E24 and S41), two positions in the distal loop (T44 and G45), and nine hydrophobic core residues has been assessed. Comparison with the Src and Spectrin SH3 domain indicates that the transition state in this protein family may be conserved. |
