Effects of dithiothreitol on the amyloid fibrillogenesis of hen egg-white lysozyme
Journal
European Biophysics Journal
Journal Volume
39
Journal Issue
8
Pages
1229-1242
Date Issued
2010
Author(s)
Abstract
At least 25 human proteins can fold abnormally to form pathological deposits that are associated with several degenerative diseases. Despite extensive investigation on amyloid fibrillation, the detailed molecular mechanisms remain rather elusive and there are currently no effective cures for treating these amyloid diseases. The present study examined the effects of dithiothreitol on the fibrillation of hen egg-white lysozyme (HEWL). Our results revealed that the fibrillation of hen lysozyme was significantly inhibited by reduced dithiothreitol (DTTred) while oxidized dithiothreitol (DTTox) had no anti-aggregating activity. Effective inhibitory activity against hen lysozyme fibrillation was observed only when DTT red was added within 8 days of incubation. Our results showed that the initial addition of DTTred interacted with HEWL, leading to a loss in conformational stability. It was concluded from our findings that DTTred-induced attenuation of HEWL fibrillation may be associated with disulfide disruption and extensive structural unfolding of HEWL. Our data may contribute to rational design of effective therapeutic strategies for amyloid diseases. ? 2010 European Biophysical Societies' Association.
Subjects
Amyloid fibril
Disulfide bond
Dithiothreitol
Inhibition
Lysozyme
Reductant
SDGs
Other Subjects
amyloid; avian protein; central nervous system agents; dithiothreitol; egg protein; egg white; lysozyme; urea; amyloid; avian protein; central nervous system agents; dithiothreitol; egg protein; lysozyme; animal; article; chemistry; chicken; drug effect; female; hydrophobicity; kinetics; metabolism; oxidation reduction reaction; protein conformation; protein folding; protein multimerization; protein stability; thermodynamics; chemical phenomena; drug effects; metabolism; protein multimerization; Amyloid; Animals; Avian Proteins; Central Nervous System Agents; Chickens; Dithiothreitol; Egg Proteins; Egg White; Female; Hydrophobicity; Kinetics; Muramidase; Oxidation-Reduction; Protein Conformation; Protein Folding; Protein Multimerization; Protein Stability; Thermodynamics; Urea; Amyloid; Animals; Avian Proteins; Central Nervous System Agents; Chickens; Dithiothreitol; Egg Proteins; Egg White; Female; Hydrophobic and Hydrophilic Interactions; Kinetics; Muramidase; Oxidation-Reduction; Protein Conformation; Protein Folding; Protein Multimerization; Protein Stability; Thermodynamics; Urea
Type
journal article