5 years ago

Hemin is able to disaggregate lysozyme amyloid fibrils into monomers

Hemin is able to disaggregate lysozyme amyloid fibrils into monomers
Lysozyme amyloidosis (ALys) is a disease of the gastrointestinal tract, liver and kidneys, which is caused by the accumulation of insoluble fibrils of lysozyme in the tissues of above organs. The ALys can be cured by disintegration and clearance of the fibrils from the affected tissues and organs. It is thought that protein fibrils are extremely stable. Consequently, small molecule-induced dissociation of fibrils under physiological conditions is really challenging. Here, we report kinetic and thermodynamic analyses of hemin-induced dissociation of hen egg white lysozyme amyloid fibrils. We examined the effect of hemin on the kinetics of dissociation of lysozyme fibrils. We observed that the hemin binding dissociates fibrils in a concentration dependent manner within a reasonable time. Studies of structural, morphological properties and gel filtration chromatography indicate that fibrils dissociate mainly into monomeric species. The conformational, hydrodynamic, unfolding and stability studies of the resolubilized proteins show that dissociated monomers possess characteristics of partially folded intermediate state of the protein. We also find that hemin-induced fibril dissociation mainly depends on the kinetic and thermodynamic stability of the fibrils. These results suggest that non-toxic derivatives of hemin and other porphyrins could pave a way for therapeutic intervention in amyloidosis and related pathologies.

Publisher URL: www.sciencedirect.com/science

DOI: S1570963917301838

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