The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin

It is known that the peptide corresponding to the N-terminal beta -hairpin of ubiquitin, U(1-17), can populate the monomeric beta -hairpin conformatio n in aqueous solution. In this study, we show that the Gly-10 that forms th e bulge of the beta -turn in this hairpin is very important to the stabilit y of the hairpin. The deletion of this residue to desG10(1-16) unfolds the structure of the peptide in water. Even under denaturing conditions, this b ulge appears to be important in maintaining the residual structure of ubiqu itin, which involves tertiary interactions within the sequence 1 to 34 in t he denatured state. We surmise that this residual structure functions as on e of the nucleation centers in the folding process and is important in stab ilizing the transition state. In accordance with this idea, deleting Gly-10 slows down the refolding and unfolding rate by about one half.