INTERACTIONS CONTRIBUTING TO THE FORMATION OF A BETA-HAIRPIN-LIKE STRUCTURE IN A SMALL PEPTIDE

A 12 amino acid peptide, model BB, was designed to adopt a beta-hairpi n tertiary structure in water that might be stabilized by a variety of local, nonlocal, polar, and nonpolar interactions. The conformational properties of model BB with and without an intramolecular disulfide b ond (BB-O and BB-R, respectively) were characterized by NMR and CD spe ctroscopy. The set of observed short- and medium-range nOes were consi stent with the formation of stable beta-hairpin-like structures by bot h BB-R and BB-O. BB-O adopts two distinct conformations that differ fr om each other in the designed reverse turn segment. A reasonably well- defined set of structures was obtained by using restraints from the NM R data in distance geometry calculations. None of the beta-hairpin-lik e structures contain a beta-sheet hydrogen bonding network. The distin ctive feature of intrastrand and cross-strand pairing of threonine res idues observed in all of the calculated structures suggests that hydro phobic interactions between the gamma-methyl groups of threonine resid ues may be the structure-determining interaction in model BB. The impl ications of these results for the formation of beta-sheets during prot ein folding, the aggregation of peptides as beta-sheets, and the de no vo design of independently folding beta-hairpin-like peptides are cons idered.