Association of apolipoprotein E with the low density lipoprotein receptor: demonstration of its co-operativity on lipid microemulsion particles.
When human apolipoprotein E (apoE), which forms a self-associated tetramer in an aqueous solution, bound to the surface of triolein/phosphatidylcholine microemulsion with a particle diameter of 26 nm, it became monomeric on the lipid particle surface without strong evidence for its accumulation on a particular particle that might be expected from its tetramer formation in the aqueous phase. ApoE in the form of the self-associated tetramer did not inhibit binding of human low density lipoprotein (LDL) to its receptor on cultured human skin fibroblast. LDL binding was inhibited only when apoE was bound to the lipid particle surface. The affinity of the apoE-containing lipid particle to the LDL receptor was of the same order as that of LDL on the basis of particle molarity when the surface of the particle was covered with apoE up to 40 to 50% of the saturation level. When the particle was covered more with apoE, the affinity increased by some 20 times. Since the surface of the lipid particle was saturated with 7 apoE molecules, the particle seemed to require to have at least 4 apoE molecules on its surface in order to obtain high binding affinity to LDL receptor.
Funahashi
T
T
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Suita, Osaka.
Yokoyama
S
S
Yamamoto
A
A
D000327:Adsorption; D001057:Apolipoproteins E / Q000032:analysis*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004655:Emulsions; D005347:Fibroblasts; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism*; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D011973:Receptors, LDL / Q000378:metabolism*; D013388:Succinimides; D014304:Triolein
D001057:Apolipoproteins E; D003432:Cross-Linking Reagents; D004655:Emulsions; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D011973:Receptors, LDL; D013388:Succinimides; D014304:Triolein; C019358:disuccinimidyl suberate