Dataset Information

Alternative Causal Link between Peptide Fibrillization and β-Strand Conformation.

ABSTRACT: In the prevailing phenomenon of peptide fibrillization, β-strand conformation has long been believed to be an important structural basis for peptide assembly. According to a widely accepted theory, in most peptide fibrillization processes, peptide monomers need to intrinsically take or transform to β-strand conformation before they can undergo ordered packing to form nanofibers. In this study, we reported our findings on an alternative peptide fibrillization pathway starting from a disordered secondary structure, which could then transform to β-strand after fibrillization. By using circular dichroism, thioflavin-T binding test, and transmission electron microscopy, we studied the secondary structure and assembly behavior of Ac-RADARADARADARADA-NH₂ (RADA16-I) in a low concentration range. The effects of peptide concentration, solvent polarity, pH, and temperature were investigated in detail. Our results showed that at very low concentrations, even though the peptide was in a disordered secondary structure, it could still form nanofibers through intermolecular assembly, and under higher peptide concentrations, the transformation from the disordered structure to β-strand could happen with the growth of nanofibers. Our results indicated that even without ordered β-strand conformation, driving forces such as hydrophobic interaction and electrostatic interaction could still play a determinative role in the self-assembly of peptides. At least in some cases, the formation of β-strand might be the consequence rather than the cause of peptide fibrillization.

SUBMITTER: Xing Z

PROVIDER: S-EPMC8154227 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:A series of designed peptides has been analyzed by 1H-NMR spectroscopy in order to investigate the influence of cross-strand side-chain interactions in beta-hairpin formation. The peptides differ in the N-terminal residues of a previously designed linear decapeptide that folds in aqueous solution into two interconverting beta-hairpin conformations, one with a type I turn (beta-hairpin 4:4) and the other with a type I + G1 beta-bulge turn (beta-hairpin 3:5). Analysis of the conformational behavior of the peptides studied here demonstrates three favorable and two unfavorable cross-strand side-chain interactions for beta-hairpin formation. These results are in agreement with statistical data on side-chain interactions in protein beta-sheets. All the peptides in this study form significant populations of the beta-hairpin 3:5, but only some of them also adopt the beta-hairpin 4:4. The formation of beta-hairpin 4:4 requires the presence of at least two favorable cross-strand interactions, whereas beta-hairpin 3:5 seems to be less susceptible to side-chain interactions. A protein database analysis of beta-hairpins 3:5 and beta-hairpins 4:4 indicates that the former occur more frequently than the latter. In both peptides and proteins, beta-hairpins 3:5 have a larger right-handed twist than beta-hairpins 4:4, so that a factor contributing to the higher stability of beta-hairpin 3:5 relative to beta-hairpin 4:4 is due to an appropriate backbone conformation of the type I + G1 beta-bulge turn toward the right-handed twist usually observed in protein beta-sheets. In contrast, as suggested previously, backbone geometry of the type I turn is not adequate for the right-handed twist. Because analysis of buried hydrophobic surface areas on protein beta-hairpins reveals that beta-hairpins 3:5 bury more hydrophobic surface area than beta-hairpins 4:4, we suggest that the right-handed twist observed in beta-hairpin 3:5 allows a better packing of side chains and that this may also contribute to its higher intrinsic stability.

Dataset Information

Alternative Causal Link between Peptide Fibrillization and β-Strand Conformation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets