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-hairpin 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 bond (BB-O and BB-R, respectively) were characterized by NMR and CD spectroscopy. The set of observed short- and medium-range nOes were consistent with the formation of stable beta-hairpin-like structures by both BB-R and BB-O. BB-O adopts two distinct conformations that differ from each other in the designed reverse turn segment. A reasonably well-defined set of structures was obtained by using restraints from the NMR data in distance geometry calculations. None of the beta-hairpin-like structures contain a beta-sheet hydrogen bonding network. The distinctive feature of intrastrand and cross-strand pairing of threonine residues observed in all of the calculated structures suggests that hydrophobic interactions between the gamma-methyl groups of threonine residues may be the structure-determining interaction in model BB. The implications of these results for the formation of beta-sheets during protein folding, the aggregation of peptides as beta-sheets, and the de novo design of independently folding beta-hairpin-like peptides are considered.
Sieber
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V
Department of Chemistry and Biochemistry, University of Delaware, Newark 19716, USA.
Moe
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GR
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004220:Disulfides; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D004220:Disulfides; D009842:Oligopeptides