Beta-amyloid peptide interacts specifically with the carboxy-terminal domain of human apolipoprotein E: relevance to Alzheimer's disease.
Growing evidence indicates the involvement of apolipoprotein E (apoE) in the development of late-onset and sporadic forms of Alzheimer's disease, although its exact role remains unclear. We previously demonstrated that beta-amyloid peptide (Abeta) displays membrane-destabilizing properties and that only apoE2 and E3 isoforms inhibit these properties. In this study, we clearly demonstrate that the carboxy-terminal lipid-binding domain of apoE (e.g., residues 200-299) is responsible for the Abeta-binding activity of apoE and that this interaction involves pairs of apoE amphipathic alpha-helices. We further demonstrate that Abeta is able to inhibit the association of the C-terminal domain of apoE with lipids due to the formation of Abeta/apoE complexes resistant to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On the contrary, the amino-terminal receptor-binding domain of apoE (e.g., residues 129-169) is not able to form stable complexes with Abeta. These data extend our understanding of human apoE-dependent binding of Abeta by involving the C-terminal domain of apoE in the efficient formation of apoE/Abeta complex.
Pillot
T
T
Laboratory for Lipoprotein Chemistry, University of Gent, Belgium.
Goethals
M
M
Najib
J
J
Labeur
C
C
Lins
L
L
Chambaz
J
J
Brasseur
R
R
Vandekerckhove
J
J
Rosseneu
M
M
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008081:Liposomes; D010446:Peptide Fragments