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Lipid membrane templates the ordering and induces the fibrillogenesis of Alzheimer's disease amyloid‐β peptide
Author(s) -
Chi Eva Y.,
Ege Canay,
Winans Amy,
Majewski Jaroslaw,
Wu Guohui,
Kjaer Kristian,
Lee Ka Yee C.
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21887
Subject(s) - chemistry , lipid bilayer , fibrillogenesis , biophysics , phospholipid , amyloid beta , vesicle , fibril , monolayer , membrane , peptide , crystallography , biochemistry , biology
The lipid membrane has been shown to mediate the fibrillogenesis and toxicity of Alzheimer's disease (AD) amyloid‐β (Aβ) peptide. Electrostatic interactions between Aβ40 and the phospholipid headgroup have been found to control the association and insertion of monomeric Aβ into lipid monolayers, where Aβ exhibited enhanced interactions with charged lipids compared with zwitterionic lipids. To elucidate the molecular‐scale structural details of Aβ‐membrane association, we have used complementary X‐ray and neutron scattering techniques (grazing‐incidence X‐ray diffraction, X‐ray reflectivity, and neutron reflectivity) in this study to investigate in situ the association of Aβ with lipid monolayers composed of either the anionic lipid 1,2‐dipalmitoyl‐sn‐glycero‐3‐[phospho‐rac‐(1‐glycerol)] (DPPG), the zwitterionic lipid 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC), or the cationic lipid 1,2‐dipalmitoyl 3‐trimethylammonium propane (DPTAP) at the air‐buffer interface. We found that the anionic lipid DPPG uniquely induced crystalline ordering of Aβ at the membrane surface that closely mimicked the β‐sheet structure in fibrils, revealing an intriguing templated ordering effect of DPPG on Aβ. Furthermore, incubating Aβ with lipid vesicles containing the anionic lipid 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐[phospho‐rac‐(1‐glycerol)] (POPG) induced the formation of amyloid fibrils, confirming that the templated ordering of Aβ at the membrane surface seeded fibril formation. This study provides a detailed molecular‐scale characterization of the early structural fluctuation and assembly events that may trigger the misfolding and aggregation of Aβ in vivo. Our results implicate that the adsorption of Aβ to anionic lipids, which could become exposed to the outer membrane leaflet by cell injury, may serve as an in vivo mechanism of templated‐aggregation and drive the pathogenesis of AD. Proteins 2008. © 2008 Wiley‐Liss, Inc.