[Supermolecular organization of apolipoprotein E in solution].

Area of Science:

• Biochemistry
• Structural Biology

Context:

• Apolipoprotein E (apoE) is crucial for lipid metabolism and transport.
• Understanding apoE's aggregation and stability is key to elucidating its role in lipoprotein assembly and disease.

Purpose:

• To investigate the aggregation behavior and solution stability of human plasma apolipoprotein E (apoE).
• To characterize the equilibrium denaturation process of fluorescein-labeled apoE using biophysical techniques.

Summary:

• Equilibrium denaturation studies revealed apoE's reversible, biphasic denaturation dependent on concentration, indicating native monomer formation.
• A proposed model suggests apoE exists in equilibrium between oligomeric, tetrameric, native monomer, and denatured monomer states.
• A monoclonal antibody (3D12F11) binds apoE with high affinity, with its epitope located away from heparin- and lipid-binding sites.

Impact:

• Postulates a two-domain structure within the apoE tetramer, with one domain involved in lipid-binding during aggregation.
• Provides insights into apoE's structural dynamics and potential implications for lipoprotein disorders.
• Characterizes antibody binding sites, aiding in the development of diagnostic or therapeutic tools targeting apoE.