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RESEARCH PRODUCT
Cholesterol Modulates the Interaction of β-Amyloid Peptide with Lipid Bilayers
Juyang HuangKwan Hon ChengJorma A. VirtanenPentti SomerharjuLiming QiuJohn ComoAnthony LewisMark W. Vaughnsubject
Time FactorsLipid BilayersMolecular Sequence DataBiophysicsPeptideFluorescence Polarization7. Clean energy03 medical and health scienceschemistry.chemical_compound0302 clinical medicineAlzheimer DiseaseErgosterolFluorescence Resonance Energy TransferAmino Acid SequenceLipid bilayer030304 developmental biologychemistry.chemical_classification0303 health sciencesLiposomeAmyloid beta-PeptidesChemistryCholesterolSterolPeptide FragmentsCrystallographyFörster resonance energy transferMembraneCholesterolCell BiophysicsTyrosinelipids (amino acids peptides and proteins)030217 neurology & neurosurgeryFluorescence anisotropyProtein Bindingdescription
The interaction of an amphiphilic, 40-amino acid beta-amyloid (Abeta) peptide with liposomal membranes as a function of sterol mole fraction (X(sterol)) was studied based on the fluorescence anisotropy of a site-specific membrane sterol probe, dehydroergosterol (DHE), and fluorescence resonance energy transfer (FRET) from the native Tyr-10 residue of Abeta to DHE. Without Abeta, peaks or kinks in the DHE anisotropy versus X(sterol) plot were detected at X(sterol) approximately 0.25, 0.33, and 0.53. Monomeric Abeta preserved these peaks/kinks, but oligomeric Abeta suppressed them and created a new DHE anisotropy peak at X(sterol) approximately 0.38. The above critical X(sterol) values coincide favorably with the superlattice compositions predicted by the cholesterol superlattice model, suggesting that membrane cholesterol tends to adopt a regular lateral arrangement, or domain formation, in the lipid bilayers. For FRET, a peak was also detected at X(sterol) approximately 0.38 for both monomeric and oligomeric Abeta, implying increased penetration of Abeta into the lipid bilayer at this sterol mole fraction. We conclude that the interaction of Abeta with membranes is affected by the lateral organization of cholesterol, and hypothesize that the formation of an oligomeric Abeta/cholesterol domain complex may be linked to the toxicity of Abeta in neuronal membranes.
year | journal | country | edition | language |
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2009-05-01 | Biophysical Journal |