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 °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 α-helical conformation to the β-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.

蛋白质纤维颤动是无数神经退行性疾病的主要原因。与原纤维形成相关的确切的潜在机制尚不清楚。最近，金属离子导致蛋白质纤维化的作用引起了科学界的关注。在这项工作中，我们采用多种生物物理和显微技术研究了铝（Al）金属离子在生理条件下对牛血清白蛋白（BSA）蛋白聚集动力学的影响。观察到色氨酸荧光的猝灭以及 9 nm 蓝移，表明 BSA 在热变性的展开途径中变得更加疏水。此外，ANS（8-苯胺基-1-萘磺酸）结合显示荧光强度随着 65 °C 孵育时间的增加而猝灭，表明去折叠导致 BSA 中疏水斑块的破坏。此外，硫黄素 T 强度表明，BSA 与 Al (III) 金属离子的比例分别为 1:1 和 1:2 时，BSA 纤维颤动显着加速。此外，圆二色性（CD）光谱研究揭示了BSA从α-螺旋构象到富含β-折叠结构的转变。分子对接分析表明 Al (III) 与涉及 Phe501、Phe506、Val575、Thr578、Gln579、Leu531 残基的 BSA 具有显着的结合亲和力 (-1.2 kcal/mol)。透射电子显微镜 (TEM) 再次证实，在 Al (III) 金属离子存在下，热诱导的 BSA 原纤维形成增强。这项研究强调了金属螯合效力作为神经系统疾病的可能治疗靶点。