Al cation induces aggregation of serum proteins

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Aluminum (Al) cation is implicated in protein fibrillation and neurodegenerative diseases.
• Understanding Al cation interactions with key proteins is crucial for disease research.

Purpose of the Study:

• To investigate the binding of Al cation to human serum albumin (HSA), bovine serum albumin (BSA), and milk beta-lactoglobulin (b-LG).
• To elucidate the thermodynamic and structural consequences of Al-protein complexation.

Main Methods:

• Spectroscopic analysis (UV-Vis, fluorescence)
• Thermodynamic analysis (isothermal titration calorimetry)
• Atomic Force Microscopy (AFM)
• Thioflavin T assay

Main Results:

• Al-protein binding is influenced by protein hydrophobicity, with beta-lactoglobulin (b-LG) showing stronger complex formation.
• Thermodynamic data suggest hydrophobic and H-bonding interactions for b-LG, and van der Waals/H-bonding for HSA and BSA.
• AFM revealed Al cations induce larger aggregates in BSA and b-LG compared to HSA.
• No significant protein fibrillation was observed via Thioflavin T testing.
• Al complexation caused conformational changes, with b-LG > BSA > HSA in terms of perturbation.

Conclusions:

• Al cation binding to serum albumins and beta-lactoglobulin alters protein conformation and promotes aggregation.
• The mechanism of interaction and aggregation depends on the specific protein's properties, particularly hydrophobicity.
• While Al induces aggregation, it does not appear to cause significant fibrillation under the tested conditions.