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Designed three-stranded beta-sheet in an alpha/beta hybrid peptide

Sonti, Rajesh and Gopi, Hosahudya N and Muddegowda, Umashankara and Ragothama, Srinivasarao and Balaram, Padmanabhan (2013) Designed three-stranded beta-sheet in an alpha/beta hybrid peptide. In: Chemistry - A European Journal, 19 (19). pp. 5955-5965.

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Official URL: http://dx.doi.org/10.1002/chem.201204327

Abstract

The incorporation of beta-amino acid residues into the antiparallel beta-strand segments of a multi-stranded beta-sheet peptide is demonstrated for a 19-residue peptide, Boc-LV(beta)FV(D)PGL(beta)FVVL(D)PGLVL(beta)FVV-OMe (BBH19). Two centrally positioned (D)Pro-Gly segments facilitate formation of a stable three-stranded beta-sheet, in which beta-phenylalanine ((beta)Phe) residues occur at facing positions 3, 8 and 17. Structure determination in methanol solution is accomplished by using NMR-derived restraints obtained from NOEs, temperature dependence of amide NH chemical shifts, rates of H/D exchange of amide protons and vicinal coupling constants. The data are consistent with a conformationally well-defined three-stranded beta-sheet structure in solution. Cross-strand interactions between (beta)Phe3/(beta)Phe17 and (beta)Phe3/Val15 residues define orientations of these side-chains. The observation of close contact distances between the side-chains on the N- and C-terminal strands of the three-stranded beta-sheet provides strong support for the designed structure. Evidence is presented for multiple side-chain conformations from an analysis of NOE data. An unusual observation of the disappearance of the Gly NH resonances upon prolonged storage in methanol is rationalised on the basis of a slow aggregation step, resulting in stacking of three-stranded beta-sheet structures, which in turn influences the conformational interconversion between type I' and type II' beta-turns at the two (D)Pro-Gly segments. Experimental evidence for these processes is presented. The decapeptide fragment Boc-LV(beta)FV(D)PGL(beta)FVV-OMe (BBH10), which has been previously characterized as a type I' beta-turn nucleated hairpin, is shown to favour a type II' beta-turn conformation in solution, supporting the occurrence of conformational interconversion at the turn segments in these hairpin and sheet structures.

Item Type: Journal Article
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Additional Information: Copyright of this article belongs to Wiley-VCH Verlag GmbH.
Keywords: Amino Acids; Hydrogen Bonds; NMR Spectroscopy; Peptides; Structure Elucidation
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Chemical Sciences > NMR Research Centre (Formerly SIF)
Date Deposited: 21 Jun 2013 05:26
Last Modified: 21 Jun 2013 05:26
URI: http://eprints.iisc.ernet.in/id/eprint/46691

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