Abstract
Protein fibrillation is a leading cause of innumerable neurodegenerative diseases. The exact underlying mechanism associated with the formation of fibrils is yet to be known. Recently, the role of metal ions resulting into fibrillation of proteins has gained attention of the scientific community. In this piece of work, we have investigated the effect of the aluminum (Al) metal ion on the kinetics of aggregation of bovine serum albumin (BSA) protein under physiological conditions by employing several biophysical and microscopic techniques. Quenching of tryptophan fluorescence was observed along with 9 nm blue shift, demonstrating BSA becomes more hydrophobic during unfolding pathway of thermal denaturation. Moreover, ANS (8-Anilino-1-naphthalene sulfonic acid) binding shows quenching in fluorescence intensity with increasing time of incubation at 65 degrees C, suggesting unfolding leading to the disruption of hydrophobic patches in BSA. Besides, Thioflavin T intensity indicated a significant acceleration in BSA fibrillation at a ratio of 1:1 and 1:2 of BSA and Al (III) metal ion respectively. In addition, circular dichroism (CD) spectroscopy study revealed the transition of BSA from alpha-helical conformation to the beta-sheet rich structure. Molecular docking analysis demonstrated significant binding affinity (-1.2 kcal/mol) of Al (III) with BSA involving Phe501, Phe506, Val575, Thr578, Gln579, Leu531 residues. Transmission electron microscopy (TEM) reaffirm augmentation of thermal-induced BSA fibril formation in the presence of Al (III) metal ions. This study highlights the metal chelating potency as the possible therapeutic target for neurological diseases. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.