Dataset Information

Rippled ?-Sheet Formation by an Amyloid-? Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric ?-Sheet Peptide Coassembly.

ABSTRACT: In 1953, Pauling and Corey predicted that enantiomeric ?-sheet peptides would coassemble into so-called "rippled" ?-sheets, in which the ?-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-? (A?) peptide that does not follow this sequence pattern, amyloid-? (16-22), readily coassembles into rippled ?-sheets. Equimolar mixtures of enantiomeric amyloid-? (16-22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated ?-sheet fibrils. Formation of rippled ?-sheets composed of alternating l- and d-amyloid-? (16-22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled ?-sheet formation by l- and d-amyloid-? (16-22) is energetically favorable relative to self-assembly into corresponding pleated ?-sheets. This work illustrates that coassembly of enantiomeric ?-sheet peptides into rippled ?-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 ?-sheet materials.

SUBMITTER: Urban JM

PROVIDER: S-EPMC6571685 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly.

Urban Jennifer M JM Ho Janson J Piester Gavin G Fu Riqiang R Nilsson Bradley L BL

Molecules (Basel, Switzerland) 20190523 10

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), rea ...[more]

PMID: 31126069

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Project description:When peptides are mixed with their mirror images in an equimolar ratio, two-dimensional periodic structural folds can form, in which extended peptide strands are arrayed with alternating chirality. The resultant topography class, termed the rippled β-sheet, was introduced as a theoretical concept by Pauling and Corey in 1953. Unlike other fundamental protein structural motifs identified around that time, including the α-helix and the pleated β-sheet, it took several decades before conclusive experimental data supporting the proposed rippled β-sheet motif were gained. Much of the key experimental evidence was provided over the course of the past decade through the concurrent efforts of our three laboratories. Studies that focused on developing new self-assembling hydrogel materials have shown that certain amphiphilic peptides form fibrils and hydrogel networks that are more rigid and have a higher thermodynamic stability when made from racemic peptide mixtures as opposed to pure enantiomers. Related interrogation of assemblies composed of mixtures of l- and d-amphiphilic peptides confirmed that the resulting fibrils were composed of alternating l/d peptides consistent with rippled β-sheets. It was also demonstrated that mirror-image amyloid beta (Aβ) could act as a molecular chaperone to promote oligomer-to-fibril conversion of the natural Aβ enantiomer, which was found to reduce Aβ neurotoxicity against different neuronal cell models. With a cross-disciplinary approach that combines experiment and theory, our three laboratories have demonstrated the unique biophysical, biochemical, and biological properties that arise upon mixing of peptide enantiomers, in consequence of rippled β-sheet formation. In this Account, we give an overview of the early history of the rippled β-sheet and provide a detailed structural description/definition of this motif relative to the pleated β-sheet. We then summarize the key findings, obtained on three unique sets of aggregating mirror-image peptide pairs through independent efforts of our three laboratories, and use these results to delineate the landscape of the rippled β-sheet structural motif to inspire future studies. Peptide sequence parameters that favor rippled β-sheet assembly are described, along with the accompanying kinetic and thermodynamic properties, as well as the resulting emergent physical properties of the assemblies. The Account then concludes with a brief overview of some key unresolved challenges in this nascent field. There is much potential for future applications of this unique supramolecular motif in the realm of materials design and biomedical research. We hope this Account will stimulate much-needed discussion of this fascinating structural class to eventually produce a fully quantitative, rational framework for the molecular engineering of rippled β-sheets in the future.

Dataset Information

Rippled ?-Sheet Formation by an Amyloid-? Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric ?-Sheet Peptide Coassembly.

Publications

Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly.

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