Formation of a membrane-active form of amyloid beta-protein in raft-like model membranes |
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Authors: | Kakio Atsuko Nishimoto Sei-ichi Kozutsumi Yasunori Matsuzaki Katsumi |
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Institution: | Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. |
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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. |
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