Lipid-bound ApoE3 self-assemble into elliptical disc-shaped particles

Area of Science:

• Biochemistry
• Structural Biology
• Lipid Metabolism

Background:

• Apolipoproteins are crucial for lipid metabolism and cholesterol transport.
• Apolipoprotein E3 (ApoE3) plays a key role in these processes.
• Understanding ApoE3's structure in lipid-bound states is vital.

Purpose of the Study:

• To structurally characterize lipid-bound particles formed by full-length and truncated ApoE3.
• To compare the lipid-binding behavior of ApoE3 with Apolipoprotein A1 (ApoA1).

Main Methods:

• Small-angle X-ray scattering (SAXS).
• Negative stain electron microscopy (EM).
• Investigation of particles formed with POPC and DMPC lipids.

Main Results:

• Lipid-bound full-length ApoE3 forms elliptical, disc-shaped particles with a central lipid bilayer and two ApoE3 proteins.
• Truncated ApoE3 (residues 80-255) forms larger, more heterogeneous discoidal particles with four proteins.
• ApoE3's truncated form shows different lipid-binding behavior compared to the analogous truncated ApoA1.

Conclusions:

• ApoE3 and ApoA1 exhibit distinct mechanisms for modulating lipid bilayer structure.
• Non-helical repeat segments of ApoE3 influence particle size and stoichiometry differently than in ApoA1.