Membrane interactions and the effect of metal ions of the amyloidogenic fragment Abeta(25-35) in comparison to Abeta(1-42).
Abeta(1-42) peptide, found as aggregated species in Alzheimer's disease brain, is linked to the onset of Alzheimer's disease. Many reports have linked metals to inducing Abeta aggregation and amyloid plaque formation. Abeta(25-35), a fragment from the C-terminal end of Abeta(1-42), lacks the metal coordinating sites found in the full-length peptide and is neurotoxic to cortical cortex cell cultures. We report solid-state NMR studies of Abeta(25-35) in model lipid membrane systems of anionic phospholipids and cholesterol, and compare structural changes to those of Abeta(1-42). When added after vesicle formation, Abeta(25-35) was found to interact with the lipid headgroups and slightly perturb the lipid acyl-chain region; when Abeta(25-35) was included during vesicle formation, it inserted deeper into the bilayer. While Abeta(25-35) retained the same beta-sheet structure irrespective of the mode of addition, the longer Abeta(1-42) appeared to have an increase in beta-sheet structure at the C-terminus when added to phospholipid liposomes after vesicle formation. Since the Abeta(25-35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity.
Lau
Tong-Lay
TL
School of Chemistry, Bio21 Institute, The University of Melbourne, VIC 3010, Australia.
Gehman
John D
JD
Wade
John D
JD
Perez
Keyla
K
Masters
Colin L
CL
Barnham
Kevin J
KJ
Separovic
Frances
F
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008670:Metals; D010446:Peptide Fragments; D010743:Phospholipids; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D002784:Cholesterol