Design and construction of an open multistranded beta-sheet polypeptide stabilized by a disulfide bridge.
The design and characterization of an open eight-stranded beta-sheet in a synthetic, 2-fold symmetric 70-residue peptide is described. The design strategy involves the generation of a 35-residue four-stranded beta-sheet peptide in which successive hairpins are nucleated by appropriately positioned (D)Pro-Xxx sequences. Oxidative dimerization using a single Cys residue positioned at the center of the C-terminal strand results in a disulfide-bridged eight-stranded structure. Nuclear Overhauser effects firmly establish an eight-stranded beta-sheet in methanol. In water, the outer strands are frayed, but a well-defined four-stranded beta-sheet stabilized by a disulfide bridge and a hydrophobic cluster is determined from NMR data. Comparison of the precursor peptide with the disulfide-bridged dimer reveals considerable enhancement of beta-sheet content in the latter, suggesting that the disulfide cross-link is an effective strategy for the stabilization of beta-sheets.
Venkatraman
Janani
J
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Nagana Gowda
Gowda A
GA
Balaram
Padmanabhan
P
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003903:Deuterium; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D014867:Water / Q000737:chemistry
D004220:Disulfides; D010455:Peptides; D014867:Water; D003903:Deuterium; D000432:Methanol