Alpha-cyclodextrin turns SDS-induced amyloid fibril into native-like structure

Abstract

Amyloid fibril formation causes multiple neurodegenerative diseases and its possible therapy is still not available. The aim of this study was to determine the solubilizing and refolding potential of α‑cyclodextrin (α-CD) on SDS-induced amyloid fibril formation of lysozyme at pH 7.4 using turbidity, intrinsic fluorescence, dynamic light scattering (DLS), ThT binding assay, far-UV circular dichroism, and molecular docking. Spectroscopic data showed that lysozyme forms amyloid-like aggregates in the presence of 0.3 mM SDS at pH 7.4. SDS-induced lysozyme fibrils were solubilized by α-CD in a dose-dependent manner. At concentrations lower than 1.0 mM, α-CD was unable to solubilize SDS-induced lysozyme fibrils, while higher concentrations of α-CD produced complete solubilization. Far-UV CD and intrinsic fluorescence data suggest that the secondary and tertiary structures of lysozyme were restored at higher α-CD concentrations. The hydrodynamic radius was found to increase in the presence of SDS and radius is restored in the presence α-CD. Molecular docking data suggest that α-CD binds the same site on lysozyme as that occupied by SDS, albeit with higher affinity. Moreover, molecular docking between SDS and α-CD shows a direct contact via hydrogen bonding between O-atom of SDS and –OH group of α-CD. We hypothesize that the higher affinity of α-CD towards the binding site on lysozyme along with its direct interaction with SDS allows it to act as a chemical chaperone displacing SDS. The mechanisms underlying this action of α-CD may provide a foundation for the identification of drugs for the suppression of fibrillogenesis.