Abstract
In 1953, Pauling and Corey predicted that enantiomeric β-sheet peptides would coassemble into so-called “rippled” β-sheets, in which the β-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-β (Aβ) peptide that does not follow this sequence pattern, amyloid-β (16–22), readily coassembles into rippled β-sheets. Equimolar mixtures of enantiomeric amyloid-β (16–22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated β-sheet fibrils. Formation of rippled β-sheets composed of alternating l- and d-amyloid-β (16–22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled β-sheet formation by l- and d-amyloid-β (16–22) is energetically favorable relative to self-assembly into corresponding pleated β-sheets. This work illustrates that coassembly of enantiomeric β-sheet peptides into rippled β-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled β-sheet materials.
Highlights
Cross-β amyloid fibrils are β-sheet rich supramolecular assemblies formed by a wide variety of peptides and proteins
We investigate whether enantiomeric peptide coassembly peptide into or ifrippled rippled β‐sheets be formed generally self‐assembling β‐strand peptide β-sheets can becan extended to a peptide that doesby notany display alternating polar/nonpolar regardless of sequence pattern
Unlike the data obtained from the l/l- fibrils, the raw solid-state nuclear nuclear magnetic magnetic resonance resonance (ssNMR) data obtained from the l/d- sample was very sharp with no shoulders as shown in Figure S5, indicating a single packing pattern of 13 C next to 19 F, and confirming the formation of rippled β-sheets with strictly alternating l/d packing structure in enantiomeric mixtures of l- and d-Aβ(16–22) as opposed to statistical mixtures as in the l-Ac-KLVFFAE-NH2 with l-Ac-KLVF(4-F-Phe)AE-NH2
Summary
Cross-β amyloid fibrils are β-sheet rich supramolecular assemblies formed by a wide variety of peptides and proteins. Enantiomeric amphipathic peptides with alternating polar/nonpolar amino acid readily self‐assemble into bilayer nanoribbon preferentially coassemble into rippled sequence patterns have been recently shownfibrils, to coassemble into rippled β-sheet materials [17,18,19,20].β‐sheets. Highlighted in green and polar side chains in purple These rippled β-sheets identified by Schneider and Nilsson are formed by similar peptides with alternating and nonpolar amino acid sequences. Nilsson peptides with coassembly of enantiomeric peptides into rippled β-sheets is unique to this class of self-assembling alternating polar and nonpolar amino acid sequences. We investigate whether enantiomeric peptide coassembly peptide into or ifrippled rippled β‐sheets be formed generally self‐assembling β‐strand peptide β-sheets can becan extended to a peptide that doesby notany display alternating polar/nonpolar regardless of sequence pattern. Aβ(16–22) would provide insight into the possibility that rippled β-sheet assembly may be a general property of all β-sheet peptides, as predicted by Pauling and Corey
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