Anionic phospholipids inhibit apolipoprotein E--low-density lipoprotein receptor interactions.
Apolipoprotein E (apoE) is a ligand for members of the low-density lipoprotein receptor (LDLR) family. Lipid-free apoE is not recognized by LDLR, yet interaction with lipid confers receptor recognition properties. Although lipid interaction is known to induce a conformational change in apoE, it is not known if the lipid composition of the resulting complex influences binding. Using reconstituted lipoprotein particles of apoE3 N-terminal (NT) domain and dimyristoylphosphatidylcholine (DMPC), maximal LDLR binding was observed at DMPC:apoE3-NT ratios >2.5:1 (w/w). ApoE3-NT lipid particles prepared with egg sphingomyelin were functional as LDLR ligands while complexes formed with the anionic phospholipids dimyristoylphosphatidylglycerol or dimyristoylphosphatidylserine (DMPS) were not. In the case of apoE3-NT, lipid particles comprised of a mixture of DMPC and DMPS, a DMPS concentration dependent inhibition of LDLR binding activity was observed. Thus, in addition to affecting apoE conformational status, the lipid composition of ligand particles can modulate LDLR binding activity.
Yamamoto
Taichi
T
Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital, Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Ryan
Robert O
RO
D000838:Anions; D001057:Apolipoproteins E / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D010715:Phosphatidylglycerols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D011973:Receptors, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000838:Anions; D001057:Apolipoproteins E; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010743:Phospholipids; D011973:Receptors, LDL; C042859:dimyristoylphosphatidylserine; C002773:dimyristoylphosphatidylglycerol