NMR analysis of amyloid-beta soluble oligomer encapsulated in reverse micelle

• Project/Area Number: 18K06151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Kyoto University
• Principal Investigator: Hoshino Masaru 京都大学, 薬学研究科, 准教授 (70304053)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アミロイドβ / 逆ミセル / 分子間相互作用 / NMR / 逆ミセル封入法 / アミロイド線維 / ＮＭＲ / 可溶性オリゴマー / 高分解能NMR

Outline of Final Research Achievements

It is difficult to analyze the process of oligomerization and fibril formation by amyloid-beta peptides, as it proceeds rapid and irreversibly. We developed the method to isolate each amyloid-beta molecule into reverse-micelle formed by AerosolAT (AOT) / n-hexane. We found that covalently-linked dimeric Abeta molecule adopted almost the same structure as that of wiled-type Abeta.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病以外にも、「アミロイド線維」という物質が蓄積することにより進行する病気は数多く存在する。どのようにして「アミロイド線維」が形成されるのかを明らかにすることは、これらの病気に共通した治療法の確立に欠かせない。本研究により「アミロイド線維」の形成反応が、分子同士の結合・解離を繰り返しつつ進行しているという様子が明らかになってきた。アルツハイマー病だけでなく、他の多くのアミロイド線維の形成機構に共通の反応だと考えられる。

Research Products

• [Journal Article] Letter to the Editor: A still unresolved mystery in the interaction between intrinsically disordered proteins: How do they recognize multiple target proteins? A commentary on “No folding upon binding of intrinsically disordered proteins: Still interesting but not unique and novel. by Sigalov, A. B., Biophysics and Physicobiology 17, 156–158 (2020). DOI: 10.2142/biophysico.BSJ-2020025” (2020)
  • Author(s): M. Hoshino
  • Journal Title: Biophysics and Physicobiology Volume: 17 Issue: 0 Pages: 159-160
  • DOI: 10.2142/biophysico.BSJ-2020028
  • NAID: 130007958012
  • ISSN: 2189-4779
  • Peer Reviewed / Open Access
• [Journal Article] A novel mode of interaction between intrinsically disordered proteins (2020)
  • Author(s): E. Hibino & M. Hoshino
  • Journal Title: Biophysics and Physicobiology Volume: 17 Issue: 0 Pages: 86-93
  • DOI: 10.2142/biophysico.BSJ-2020012
  • NAID: 130007889459
  • ISSN: 2189-4779
  • Peer Reviewed / Open Access
• [Journal Article] Toxic amyloid tape: A novel mixed antiparallel/parallel beta-sheet structure formed by amyloid beta-protein on GM1 clusters. (2019)
  • Author(s): Y. Okada, K. Okubo, K. Ikeda, Y. Yano, M. Hoshino, Y. Hayashi, Y. Kiso, H. Itoh-Watanabe, A. Naito & K. Matsuzaki
  • Journal Title: ACS Chem. Neurosci. Volume: 10 Issue: 1 Pages: 563-572
  • DOI: 10.1021/acschemneuro.8b00424
  • Peer Reviewed
• [Journal Article] Structural characterization of the N-terminal kinase-interacting domain of an Hsp90-cochaperone Cdc37 by CD and solution NMR spectroscopy. (2019)
  • Author(s): Ihama, F., Yamamoto, M., Kojima, C., Fujiwara, T., Matsuzaki, K., Miyata, Y., Hoshino, M.
  • Journal Title: Biochim. Biophys. Acta-Proteins Proteom. Volume: 1867 Issue: 9 Pages: 813-820
  • DOI: 10.1016/j.bbapap.2019.06.007
  • Peer Reviewed
• [Journal Article] Novel Interaction Mechanism between the Intrinsically Disordered Proteins (2019)
  • Author(s): 日比野 絵美, 星野 大
  • Journal Title: Seibutsu Butsuri Volume: 59 Issue: 4 Pages: 202-204
  • DOI: 10.2142/biophys.59.202
  • NAID: 130007683547
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed
• [Journal Article] Not Oligomers but Amyloids are Cytotoxic in the Membrane-Mediated Amyloidogenesis of Amyloid-beta Peptides. (2018)
  • Author(s): N. Itoh, E. Takada, K. Okubo, Y. Yano, M. Hoshino, A. Sasaki, M. Kinjo & K. Matsuzaki
  • Journal Title: ChemBioChem Volume: 19 Issue: 5 Pages: 430-433
  • DOI: 10.1002/cbic.201700576
  • Peer Reviewed
• [Journal Article] Use of a compact tripodaltris(bipyridine) ligand to stabilize a single metal-centered chirality: stereoselective coordination of iron(II) and ruthenium(II) on a semi-rigid hexapeptide macrocycle. (2018)
  • Author(s): Y.Kobayashi, M. Hoshino, T. Kameda, K. Kobayashi, K. Akaji, S. Inuki, H. Ohno & S. Oishi
  • Journal Title: Inorg. Chem. Volume: 57 Issue: 9 Pages: 5475-5485
  • DOI: 10.1021/acs.inorgchem.8b00416
  • Peer Reviewed
• [Presentation] Interaction between Mint3 and FIH-1 analyzed by high-resolution NMR (2020)
  • Author(s): Ryo Maeda, Satoru Nagatoishi, Kouhei Tsumoto, Katsumi Matsuzaki & Masaru Hoshino
  • Organizer: 第20回日本蛋白質科学会年会
• [Presentation] Dynamic equilibrium between amyloid-β molecules required for "mature" fibril formation. (2019)
  • Author(s): M. Hoshino
  • Organizer: Pavia Meeting
  • Int'l Joint Research
• [Presentation] 高分解能溶液NMRによるタンパク質の動的構造解析 (2019)
  • Author(s): 星野 大
  • Organizer: 第20回若手NMR研究会
  • Invited
• [Presentation] Dynamic equilibrium between oligomeric states of amyloid-β peptide studied by solution NMR (2019)
  • Author(s): Masaru Hoshino
  • Organizer: The 3rd Ulm Meeting - Biophysics of Amyloid Formation
  • Int'l Joint Research
• [Presentation] 高分解能溶液NMRによるアミロイドβ凝集初期過程の解析 (2018)
  • Author(s): 中川 大雅、西井 一郎、松崎 勝巳、星野 大
  • Organizer: 第18回日本蛋白質科学会年会
• [Presentation] シャペロニンGroEのフットボール型複合体におけるリング交換反応 (2018)
  • Author(s): 石野 聡、矢野 義明、河田 康志、松崎 勝巳、星野 大
  • Organizer: 第91回日本生化学会大会
• [Presentation] アミロイドβペプチド凝集初期過程の解析 (2018)
  • Author(s): 星野 大、中川 大雅、釣 大佑、西井 一郎
  • Organizer: 第10回 タンパク質の異常凝集とその防御・修復機構に関する研究会