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ID 112401
Mizuguchi, Chiharu Kyoto Pharmaceutical University|Tokushima University
Nakamura, Mitsuki Kyoto Pharmaceutical University
Kurimitsu, Naoko Kyoto Pharmaceutical University
Ohgita, Takashi Kyoto Pharmaceutical University
Baba, Teruhiko National Institute of Advanced Industrial Science and Technology (AIST)
Shimanouchi, Toshinori Okayama University
Saito, Hiroyuki Kyoto Pharmaceutical University KAKEN Search Researchers
Content Type
Journal Article
Here, we examined the effects of phosphatidylserine (PS) and cholesterol on the fibril-forming properties of the N-terminal 1‒83 fragment of an amyloidogenic G26R variant of apoA-I bound to small unilamellar vesicles. A thioflavin T fluorescence assay together with microscopic observations showed that PS significantly retards the nucleation step in fibril formation by apoA-I 1‒83/G26R, whereas cholesterol slightly enhances fibril formation. Circular dichroism analyses demonstrated that PS facilitates a structural transition from random coil to α-helix in apoA-I 1‒83/G26R with great stabilization of the α-helical structure upon lipid binding. Isothermal titration calorimetry measurements revealed that PS induces a marked increase in capacity for binding of apoA-I 1‒83/G26R to the membrane surface, perhaps due to electrostatic interactions of positively charged amino acids in apoA-I with PS. Such effects of PS to enhance lipid interactions and inhibit fibril formation of apoA-I were also observed for the amyloidogenic region-containing apoA-I 8‒33/G26R peptide. Fluorescence measurements using environment-sensitive probes indicated that PS induces a more solvent-exposed, membrane-bound conformation in the amyloidogenic region of apoA-I without affecting membrane fluidity. Since cell membranes have highly heterogeneous lipid compositions, our findings may provide a molecular basis for the preferential deposition of apoA-I amyloid fibrils in tissues and organs.
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Scientific Reports
Springer Nature
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Supplementary Information : srep_8_5497_s1.docx
© The Author(s) 2018
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Medical Sciences
Pharmaceutical Sciences