title: Copper(II) directs formation of toxic amorphous aggregates resulting in inhibition of hen egg white lysozyme fibrillation under alkaline salt-mediated conditions.
abstract: Hen egg white lysozyme (HEWL) adopts a molten globule-like state at high pH (~12.75) and is found to form amyloid fibrils at alkaline pH. Here, we report that Cu(II) inhibits self-association of HEWL at pH 12.75 both at 37 and 65 °C. A significant reduction in Thioflavin T fluorescence intensity, attenuation in β-sheet content and reduction in hydrophobic exposure were observed with increasing Cu(II) stoichiometry. Electron paramagnetic resonance spectroscopy suggests a 4N type of coordination pattern around Cu(II) during fibrillation. Cu(II) is also capable of altering the cytotoxicity of the proteinaceous aggregates. Fibrillar species of diverse morphology were found in the absence of Cu(II) with the generation of amorphous aggregates in the presence of Cu(II), which are more toxic compared to the fibrils alone.
authors.affiliation: a Department of Chemistry , Indian Institute of Technology , Kharagpur 721302 , India.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Ghosh
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Pandey
authors.forename: Priyanka
authors.initials: P
authors.lastname: Banerjee
authors.forename: Koel
authors.initials: K
authors.lastname: Chaudhury
authors.forename: Nóra Veronika
authors.initials: NV
authors.lastname: Nagy
authors.forename: Swagata
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D066329:Protein Aggregates; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D013696:Temperature
chemical_list: D000682:Amyloid; D066329:Protein Aggregates; D012965:Sodium Chloride; D003300:Copper; C421864:hen egg lysozyme; D009113:Muramidase
keywords: Cu(II) stoichiometry; cytotoxicity; fibrillation; hen egg white lysozyme; inhibition; molten globule state