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 n...

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Bibliographic Details
Published inBiochemical and biophysical research communications Vol. 354; no. 3; pp. 820 - 824
Main Authors Yamamoto, Taichi, Ryan, Robert O.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 16.03.2007
Subjects
Anionic phospholipid
Anions
Apolipoprotein E
Apolipoproteins E - antagonists & inhibitors
Apolipoproteins E - metabolism
Binding, Competitive
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Fluorescence
Low-density lipoprotein receptor
Phosphatidylglycerols - pharmacology
Phosphatidylserines - pharmacology
Phospholipids - pharmacology
Receptors, LDL - antagonists & inhibitors
Receptors, LDL - metabolism
DMPG
apo
sDLR
EGF
NT
Fluorescence
DMPS
AEDANS
Apolipoprotein E
Anionic phospholipid
FRET
DMPC
Low-density lipoprotein receptor
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.01.066