Amyloid-beta peptide disruption of lipid membranes and the effect of metal ions.
Beta-amyloid peptide (Abeta), which is cleaved from the larger trans-membrane amyloid precursor protein, is found deposited in the brain of patients suffering from Alzheimer's disease and is linked with neurotoxicity. We report the results of studies of Abeta1-42 and the effect of metal ions (Cu2+ and Zn2+) on model membranes using 31P and 2H solid-state NMR, fluorescence and Langmuir Blodgett monolayer methods. Both the peptide and metal ions interact with the phospholipid headgroups and the effects on the lipid bilayer and the peptide structure were different for membrane incorporated or associated peptides. Copper ions alone destabilise the lipid bilayer and induced formation of smaller vesicles but when Abeta1-42 was associated with the bilayer membrane copper did not have this effect. Circular dichroism spectroscopy indicated that Abeta1-42 adopted more beta-sheet structure when incorporated in a lipid bilayer in comparison to the associated peptide, which was largely unstructured. Incorporated peptides appear to disrupt the membrane more severely than associated peptides, which may have implications for the role of Abeta in disease states.
Lau
Tong-Lay
TL
School of Chemistry, The University of Melbourne, Melbourne, Vic. 3010, Australia.
Ambroggio
Ernesto E
EE
Tew
Deborah J
DJ
Cappai
Roberto
R
Masters
Colin L
CL
Fidelio
Gerardo D
GD
Barnham
Kevin J
KJ
Separovic
Frances
F
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity; D002413:Cations, Divalent / Q000737:chemistry; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C075222:amyloid beta-protein (1-42); C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D003300:Copper; D015032:Zinc; C028694:1-palmitoyl-2-oleoylphosphatidylcholine