title: Fibrillation of human serum albumin shows nonspecific coordination on stoichiometric increment of Copper(II).
abstract: Protein aggregation is related to a series of pathological disorders the main cause of which are the fibrillar species generated during the process. Human serum albumin (HSA) undergoes rapid fibrillation in the presence of Cu(II) at pH 7.4 in 60% ethanol after 6-h incubation (∼65 °C) followed by room temperature incubation. Here, we have investigated the effect of a stoichiometric variation of Cu(II) on the self-assembly of HSA using Congo red and thioflavin T dye-binding studies, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, electron paramagnetic resonance spectroscopy, fluorescence microscopy and transmission electron microscopy. The simulation of EPR spectra suggests that with the increment in Cu(II) ion concentration, there is a change in ligand field coordination. Kinetic parameters indicate reduced cooperativity that may be related to the nonspecific coordination on increment of Cu(II) concentration. Cu(II) is also able to direct the accumulation of a large number of fibers along with a formation of dense fibrillar network which is evident from microscopic images.
authors.affiliation: a Department of Chemistry , Indian Institute of Technology , Kharagpur 721302 , India .
authors.forename: Nitin Kumar
authors.initials: NK
authors.lastname: Pandey
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Ghosh
authors.forename: Nóra Veronika
authors.initials: NV
authors.lastname: Nagy
authors.forename: Swagata
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D052160:Benzothiazoles; D003224:Congo Red / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D066329:Protein Aggregates; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D052160:Benzothiazoles; D056831:Coordination Complexes; D066329:Protein Aggregates; D012709:Serum Albumin; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red; D003300:Copper
keywords: Cu(II); aggregation; fibrillation; human serum albumin; stoichiometry