Novel Approach of Solid-State NMR to Reveal Molecular Mechanism of Supramolecular Structural Formation of Biomolecules Through Lipid Bilayers

• Project/Area Number: 16K05858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Institute for Molecular Science
• Principal Investigator: Nishimura Katsuyuki 分子科学研究所, 物質分子科学研究領域, 准教授 (00334631)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 固体NMR / アミロイドβ / オリゴマー / 脂質膜 / 構造解析 / 生体分子 / 脂質 / アミロイド / 開発

Outline of Final Research Achievements

We have explored to develop effective techniques of solid-state NMR for structural characterizations of peripheral membrane proteins and peptides which express their functions based on their supramolecular structures conformed by associations among them and interactions with lipid bilayers. On the other hand, amyloid-β has been considered to play crucial roles in the onset and developments of Alzheimer's disease through the fomation of insoluble amyloid fibrils. In this study, we have also explored structural characterization of oligomeric state amyloid-β(1-40) induced on model neuronal lipid membranes based on solid-state NMR.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は、多くの国民に直接関わる重要な疾患であるが、その発症機構の解明、および完治可能な治療薬の開発には至っていない。当該疾患の発症に深く関与することが示唆されているアミロイドβが形成する不溶性アミロイド線維形成の分子機構解明は、同疾患治療および予防の実現に必要不可欠な研究課題である。本研究は、この解明に大きく寄与することが期待され、学術的、社会的にもその意義は大きいと考えられる。

Research Products

• [Int'l Joint Research] The City University of New York(米国)
• [Journal Article] Effective Synthesis and Their Copolymerization of Fluorine-Containing Phenanthrene with Hydroxyl Group (2019)
  • Author(s): S. Kataoka, H. Fukumoto, T. Kawasaki-Takasuka, T. Yamazaki, K. Nishimura, T. Agou, T. Kubota
  • Journal Title: Journal Fluorine Chemistry Volume: 218 Pages: 84-89
  • DOI: 10.1016/j.jfluchem.2018.11.017
  • Peer Reviewed
• [Journal Article] Quantitative Analysis of Solid-State Homonuclear Correlation Spectra of Antiparallel beta-Sheet Alanine Tetramers (2018)
  • Author(s): A. Naito, K. Okushita, K. Nishimura, G. S. Boutis, A. Aoki, and T. Asakura
  • Journal Title: J. Phys. Chem. B Volume: 122 Issue: 10 Pages: 2715-2724
  • DOI: 10.1021/acs.jpcb.7b11126
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Helix-in-Helix" Superstructure Formation through Encapsulation of Fullerene-Bound Helical Peptides within a Helical Poly(Methyl Methacrylate) Cavity (2017)
  • Author(s): N. Ousaka, F. Mamiya, Y. Iwata, Y. Nishimura, E. Yashima
  • Journal Title: Angew. Chem., Int. Ed. Volume: 56 Issue: 3 Pages: 791-795
  • DOI: 10.1002/anie.201611349
  • Peer Reviewed / Open Access
• [Journal Article] Molecular and electron-spin structures of a ring-shaped mixed-valence polyoxovanadate (IV, V) studied by 11B and 23Na solid-state NMR spectroscopy and DFT calculations (2016)
  • Author(s): Takahiro Iijima, Toshihiro Yamase, Katsuyuki Nishimura
  • Journal Title: Solid State Nuclear Magnetic Resonance Volume: 76-77 Pages: 15-23
  • DOI: 10.1016/j.ssnmr.2016.03.004
  • Peer Reviewed
• [Journal Article] Multiple-component covalent organic frameworks (2016)
  • Author(s): N. Huang, L. Zhai, D. E. Coupry, M. A. Addicoat, K. Okushita, K. Nishimura, T. Heine, D. Jiang
  • Journal Title: Nat. Comm Volume: 7 Issue: 1
  • DOI: 10.1038/ncomms12325
  • Peer Reviewed / Open Access
• [Journal Article] Structure and Dynamics of Membrane-Bound Proteins (2016)
  • Author(s): K. Nishimura, M. Tanio, and S. Tuzi
  • Journal Title: Modern Magnetic Resonance Volume: - Pages: 1-13
  • DOI: 10.1007/978-3-319-28275-6_62-1
  • ISBN: 9783319282756
• [Presentation] 固体NMR法によるGM1ガングリオシド膜上におけるアミロイドβの構造解析 (2019)
  • Author(s): 矢木真穂，西村勝之, 加藤晃一
  • Organizer: 日本薬学会第139年会
• [Presentation] 固体 NMR 法を用いたガングリオシド膜上におけるアミロイドβの構造解析 (2018)
  • Author(s): 矢木真穂，加藤晃一，西村勝之
  • Organizer: 第57回 NMR討論会
• [Presentation] NMR Characterization of Conformational Transition of Amyloid-β Promoted in Membrane Environments (2016)
  • Author(s): Maho Yagi-Utsumi, Katsuyuki Nishimura, Koichi Kato
  • Organizer: 27th International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: 国立京都国際会館 (京都府 京都市)
  • Year and Date: 2016-08-21