論文

査読有り 国際誌
2018年4月3日

Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I.

Scientific reports
  • Chiharu Mizuguchi
  • Mitsuki Nakamura
  • Naoko Kurimitsu
  • Takashi Ohgita
  • Kazuchika Nishitsuji
  • Teruhiko Baba
  • Akira Shigenaga
  • Toshinori Shimanouchi
  • Keiichiro Okuhira
  • Akira Otaka
  • Hiroyuki Saito
  • 全て表示

8
1
開始ページ
5497
終了ページ
5497
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-018-23920-3
出版者・発行元
NATURE PUBLISHING GROUP

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.

リンク情報
DOI
https://doi.org/10.1038/s41598-018-23920-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29615818
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882889
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000428999200033&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41598-018-23920-3
  • ISSN : 2045-2322
  • PubMed ID : 29615818
  • PubMed Central 記事ID : PMC5882889
  • Web of Science ID : WOS:000428999200033

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