title: Formation of a membrane-active form of amyloid beta-protein in raft-like model membranes.
abstract: The conversion of soluble, nontoxic amyloid beta-protein (A beta) to aggregated, toxic A beta rich in beta-sheet structures is considered to be the key step in the development of Alzheimer's disease. We have proposed that the aggregation proceeds in the lipid raft containing a ganglioside cluster, the formation of which is facilitated by cholesterol and for which A beta shows a specific affinity. In this study, using fluorescence resonance energy transfer, we found that after A beta binds to raft-like membranes composed of monosialoganglioside GM1/cholesterol/sphingomyelin (1/1/1), the protein can translocate to the phosphatidylcholine membranes to which soluble A beta does not bind. Furthermore, self-quenching experiments using fluorescein-labeled A beta revealed that the translocation process competes with the oligomerization of the protein in the raft-like membranes. These results suggest that the lipid raft containing a ganglioside cluster serves as a conformational catalyst or a chaperon generating a membrane-active form of A beta with seeding ability.
authors.affiliation: Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kakio
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Nishimoto
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kozutsumi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D002784:Cholesterol; D005677:G(M1) Ganglioside; D006801:Humans; D007700:Kinetics; D021962:Membrane Microdomains / Q000378:metabolism*; D008567:Membranes, Artificial; D008954:Models, Biological; D008958:Models, Molecular; D010713:Phosphatidylcholines; D017433:Protein Structure, Secondary; D021381:Protein Transport; D013050:Spectrometry, Fluorescence; D013109:Sphingomyelins
chemical_list: D016229:Amyloid beta-Peptides; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D005677:G(M1) Ganglioside; D002784:Cholesterol