Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• The VLDL receptor is a newly identified lipoprotein receptor.
• It recognizes lipoproteins containing apolipoprotein E (apoE).
• Chinese hamster ovary (CHO) cells lacking LDL receptors (1d1A-7) were used to study VLDL receptor function.

Purpose of the Study:

• To investigate the binding characteristics of the VLDL receptor.
• To compare the apoE binding site on the VLDL receptor with that on the LDL receptor.

Main Methods:

• Overexpression of the human VLDL receptor in 1d1A-7 CHO cells.
• Competition assays using VLDL from normolipidemic subjects with different apoE alleles (epsilon3, epsilon2).
• Use of an anti-apoE monoclonal antibody (1D7) to probe binding interactions.

Main Results:

• VLDL containing apoE3 or apoE2 competed for radiolabeled beta-VLDL binding to VLDL receptors.
• The anti-apoE antibody 1D7, which blocks apoE binding to LDL receptors, did not inhibit VLDL binding to VLDL receptors.
• This suggests that the apoE binding site on the VLDL receptor is distinct from that on the LDL receptor.

Conclusions:

• The VLDL receptor recognizes apoE-containing lipoproteins.
• The binding site for apoE on the VLDL receptor differs from its binding site on the LDL receptor.
• These findings highlight distinct molecular mechanisms in lipoprotein recognition by different receptors.