title: Anionic phospholipids inhibit apolipoprotein E--low-density lipoprotein receptor interactions.
abstract: 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.
authors.affiliation: 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.
authors.forename: Taichi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
mesh_terms: 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
chemical_list: D000838:Anions; D001057:Apolipoproteins E; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010743:Phospholipids; D011973:Receptors, LDL; C042859:dimyristoylphosphatidylserine; C002773:dimyristoylphosphatidylglycerol