Apolipoprotein E includes a binding site which is recognized by several amyloidogenic polypeptides.
Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is a risk factor for late-onset Alzheimer's disease (AD). Biochemically apoE is present in AD plaques and neurofibrillary tangles of the AD brain. There is a high avidity and specific binding of apoE and the amyloid beta-peptide (A beta). In addition to AD apoE is also present in many other cerebral and systemic amyloidoses, Down's syndrome and prion diseases but the pathophysiological basis for its presence is still unknown. In the present study we have compared the interaction of apoE with A beta, the gelsolin-derived amyloid fragment AGel(183-210) and the amyloidogenic prion fragments PrP(109-122) and PrP(109-141). We show that, similar to A beta, also AGel and PrP fragments can form a complex with apoE, and that the interaction between apoE and the amyloidogenic protein fragments is mediated through the same binding site on apoE. We also show that apoE increases the thioflavin-T fluorescence of PrP and AGel and that apoE influences the content of beta-sheet conformation of these amyloidogenic fragments. Our results indicate that amyloids and amyloidogenic prion fragments share a similar structural motif, which is recognized by apoE, possibly through a single binding site, and that this motif is also responsible for the amyloidogenicity of these fragments.
Baumann
M H
MH
Institute of Biomedicine, Protein Chemistry Education and Research Unit, P.O. Box 8, FIN-00014 University of Helsinki, Finland. Marc.Baumann@helsinki.fi
Kallijärvi
J
J
Lankinen
H
H
Soto
C
C
Haltia
M
M
D020816:Amino Acid Motifs; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000686:Amyloidosis / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010455:Peptides