On the Aggregation of Apolipoprotein A-I

Area of Science:

• Biochemistry
• Molecular Biology
• Protein Aggregation

Background:

• Apolipoprotein A-I (ApoA-I) is found in lipoprotein particles and is associated with diseases like atherosclerosis and amyloidosis.
• Deposited ApoA-I forms amyloid fibrils, suggesting a role in disease development.

Purpose of the Study:

• Investigate ApoA-I aggregation into amyloid fibrils and other morphologies.
• Study wildtype ApoA-I and the disease-associated mutant ApoA-I K107Δ under various conditions.

Main Methods:

• Thioflavin T fluorescence intensity assay to monitor aggregation.
• Circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, and cryo-transmission electron microscopy for aggregate characterization.

Main Results:

• ApoA-I can form globular protein-only condensates retaining α-helical structure.
• Wildtype ApoA-I is resistant to amyloid formation unless oxidized or mutated.
• The K107Δ mutant exhibits increased amyloid formation propensity, forming both amyloid fibrils and condensates.

Conclusions:

• Oxidation and specific mutations, like K107Δ, promote ApoA-I conversion to amyloid fibrils.
• ApoA-I aggregation can result in a mixture of amyloid fibrils and stable condensates.