Heme binding site in apomyoglobin may be effectively targeted with small molecules to control aggregation

Area of Science:

• Biochemistry
• Protein aggregation
• Metalloproteins

Background:

• Protein aggregation is implicated in various diseases.
• Apomyoglobin aggregation can lead to amorphous and fibrillar structures.
• Controlling protein aggregation is a significant therapeutic challenge.

Purpose of the Study:

• To investigate the efficacy of heme-binding ligands in controlling apomyoglobin aggregation.
• To assess the structural and cytotoxic effects of ligand-mediated aggregation control.
• To determine if structural similarity to heme influences ligand effectiveness.

Main Methods:

• Ligand screening for heme binding site affinity.
• Employing fluorescence, dynamic light scattering, and transmission electron microscopy for structural analysis.
• Utilizing dot blot analysis and viability studies for cytotoxicity assessment.

Main Results:

• Chrysin and Nile red, structurally similar to heme, were identified as effective modulators.
• Nile red inhibited fibrillar aggregation, while chrysin prevented both amorphous and fibrillar forms.
• Ligands influenced aggregation at distinct intermediate stages, correlating with heme structural similarity.

Conclusions:

• Heme-mimicking ligands can effectively control protein aggregation pathways.
• This strategy holds broad applicability for metalloproteins, which represent a large protein class.
• Ligand-induced modulation of protein aggregation offers a promising therapeutic avenue.