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Mechanism and regulation of protein aggregation in complicated cellular systems

Research Project

Project/Area Number 15H04362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biophysics
Research InstitutionOsaka University

Principal Investigator

Goto Yuji  大阪大学, たんぱく質研究所, 教授 (40153770)

Co-Investigator(Kenkyū-buntansha) 櫻井 一正  近畿大学, 先端技術総合研究所, 准教授 (10403015)
Co-Investigator(Renkei-kenkyūsha) OGI HIROTSUGU  大阪大学, 大学院工学研究科, 教授 (90252626)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords蛋白質 / 脳神経変性疾患 / 生体分子 / 凝集 / 変性 / アミロイド線維 / 溶解度 / 過飽和 / 蛋白質凝集 / 相転移 / 老化 / 脳神経疾患 / アミロイド凝集
Outline of Final Research Achievements

Understanding the mechanisms of protein aggregation is important for advancing our knowledge of proteins. Amyloid fibrils are fibrillar aggregates associated with various amyloidoses. On the other hand, the term amorphous aggregate has been used for other types of aggregates. However, the relationship between amyloid fibrils and amorphous aggregates has not yet been elucidated. We studied the aggregation of various proteins with a focus on distinguishing amyloid fibrils and amorphous aggregates. The results indicated that amyloid fibrils and amorphous aggregates correspond to crystals and glasses of solutes, respectively, and that solubility and supersaturation are two of the most important factors determining protein aggregation. Further understanding the role of supersaturation in determining aggregation-based phase transitions of denatured proteins will provide an important complementary point of view to structural studies of protein aggregates.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (47 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (12 results) Journal Article (17 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 17 results,  Open Access: 7 results,  Acknowledgement Compliant: 7 results) Presentation (15 results) (of which Int'l Joint Research: 9 results,  Invited: 15 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] エトバッシュローランド大学(ハンガリー)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ユニバーシティ・カレッジ・ロンドン(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ウディネ大学/パビア大学(イタリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ミュンヘン工科大学(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] オーストラリア国立大学(オーストラリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] エトバッシュローランド大学(ハンガリー)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ユニバーシティ・カレッジ・ロンドン(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ウディネ大学/パビア大学(イタリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Eotvos Lorand University(ハンガリー)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Australian National University(オーストラリア)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Technische Universitat Munchen(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A new look at an old view of denaturant induced protein unfolding2018

    • Author(s)
      Hall Damien、Kinjo Akira R.、Goto Yuji
    • Journal Title

      Analytical Biochemistry

      Volume: 542 Pages: 40-57

    • DOI

      10.1016/j.ab.2017.11.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Non-native alpha-helices in the initial folding intermediate facilitate the ordered assembly of the beta-barrel in beta-lactoglobulin2017

    • Author(s)
      Sakurai, K., Yagi, M., Konuma, T., Takahashi, S., Nishimura, C., Goto, Y.
    • Journal Title

      Biochemistry

      Volume: 56 Issue: 36 Pages: 4799-4807

    • DOI

      10.1021/acs.biochem.7b00458

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nanoscale Dynamics of Protein Assembly Networks in Supersaturated Solutions2017

    • Author(s)
      Matsushita Y.、Sekiguchi H.、Wong C. Jae、Nishijima M.、Ikezaki K.、Hamada D.、Goto Y.、Sasaki Y. C.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 13883-13883

    • DOI

      10.1038/s41598-017-14022-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation2017

    • Author(s)
      Nitani Ayame、Muta Hiroya、Adachi Masayuki、So Masatomo、Sasahara Kenji、Sakurai Kazumasa、Chatani Eri、Naoe Kazumitsu、Ogi Hirotsugu、Hall Damien、Goto Yuji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 52 Pages: 21219-21230

    • DOI

      10.1074/jbc.m117.813097

    • NAID

      120006557632

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Salt-induced formations of partially folded intermediates and amyloid fibrils suggests a common underlying mechanism2017

    • Author(s)
      Goto Yuji、Adachi Masayuki、Muta Hiroya、So Masatomo
    • Journal Title

      Biophysical Reviews

      Volume: 10 Issue: 2 Pages: 493-502

    • DOI

      10.1007/s12551-017-0370-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparin-induced amyloid fibrillation of beta2-microglobulin explained by solubility and a supersaturation-dependent conformational phase diagram.2017

    • Author(s)
      So, M., Hata, Y., Naiki, H. and Goto, Y.
    • Journal Title

      Protein Science

      Volume: 26 Issue: 5 Pages: 1024-1036

    • DOI

      10.1002/pro.3149

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Optimized ultrasonic irradiation finds out ultra-stable Abeta1-40 oligomer.2017

    • Author(s)
      Nakajima, K., So, M., Takahashi, K., Tagawa, Y., Hirao, M., Goto, Y. and Ogi, H.
    • Journal Title

      J. Phys. Chem. B

      Volume: 121 Issue: 12 Pages: 2603-2613

    • DOI

      10.1021/acs.jpcb.7b01409

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Drastic acceleration of fibrillation of insulin by transient cavitation bubble2017

    • Author(s)
      Nakajima, K., Nishioka, D., Hirao, M., So, M., Goto, Y., Ogi, H.
    • Journal Title

      Ultrason. Sonochem.

      Volume: 36 Pages: 206-211

    • DOI

      10.1016/j.ultsonch.2016.11.034

    • NAID

      120007148339

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thioflavin T-silent denaturation intermediates support the main-chain dominated architecture of amyloid fibrils.2016

    • Author(s)
      Noda, S., So, M., Adachi, M., Kardos, J., Akazawa-Ogawa, Y., Hagihara, H., and Goto, Y.
    • Journal Title

      Biochemistry

      Volume: 55 Issue: 28 Pages: 3937-3948

    • DOI

      10.1021/acs.biochem.6b00231

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Recognizing and analyzing variability in amyloid formation kinetics: Simulation and statistical methods.2016

    • Author(s)
      Hall, D., Zhao, R., So, M., Adachi, M., Rivas, G., Carver, J. A. and Goto, Y.
    • Journal Title

      Anal. Biochem.

      Volume: 510 Pages: 56-71

    • DOI

      10.1016/j.ab.2016.07.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] タンパク質凝集の新たな理解―タンパク質凝集を支配するオストワルドの段階則2016

    • Author(s)
      池之上達哉、後藤祐児
    • Journal Title

      化学

      Volume: 71 Pages: 70-71

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Revisiting supersaturation as a factor determining amyloid fibrillation.2016

    • Author(s)
      So, M., Hall, D. and Goto, Y.
    • Journal Title

      Curr. Opin. Struct. Biol.

      Volume: 36 Pages: 32-39

    • DOI

      10.1016/j.sbi.2015.11.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nucleus factory on cavitation bubble for amyloid β fibril.2016

    • Author(s)
      Nakajima, K., Ogi, H., Adachi, K., Noi, K., Hirao, M., Yagi, H. and Goto, Y.
    • Journal Title

      Sci. Rep.

      Volume: 6 Pages: 22015-22015

    • NAID

      120006557627

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Supersaturation-limited and unlimited phase spaces compete to produce maximal amyloid fibrillation near the critical micelle concentration of sodium dodecyl sulfate.2015

    • Author(s)
      So, M., Ishii, A., Hata, Y., Yagi, H., Naiki, H. and Goto, Y.
    • Journal Title

      Langmuir

      Volume: 31(36) Issue: 36 Pages: 9973-9982

    • DOI

      10.1021/acs.langmuir.5b02186

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Synchrotron FTIR Micro-Spectroscopy for Structural Analysis of Lewy Bodies in the Brain of Parkinson’s Disease Patients2015

    • Author(s)
      K. Araki, N. Yagi, Y. Ikemoto, S. Choong, H. Hayakawa, G. Beck, H. Sumi, H. Fujimura, T. Moriwaki, Y. Nagai, Y. Goto and H. Mochizuki
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 17625-17625

    • DOI

      10.1038/srep17625

    • NAID

      120006557628

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation.2015

    • Author(s)
      Adachi, M. So, M., Sakurai, K., Kardos, J. and Goto, Y.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 (29) Issue: 29 Pages: 18134-18145

    • DOI

      10.1074/jbc.m115.648139

    • NAID

      120006557633

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A multi-pathway perspective on protein aggregation: Implications for control of the rate and extent of amyloid formation.2015

    • Author(s)
      Hall, D., Kardos, J., Edskes, H., Carver, J. A. and Goto Y.
    • Journal Title

      FEBS Lett.

      Volume: 589(6), Issue: 6 Pages: 672-679

    • DOI

      10.1016/j.febslet.2015.01.032

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 超音波に依存した蛋白質過飽和溶液の相転移現象2017

    • Author(s)
      後藤祐児
    • Organizer
      日本物理学会第72回年次大会シンポジウム
    • Place of Presentation
      大阪大学(大阪府、豊中市)
    • Year and Date
      2017-03-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Revisiting supersaturation as a factor determining amyloid fibrillation.2017

    • Author(s)
      Goto, Yuji
    • Organizer
      The 2nd Joint Symposium of IPR, Osaka University, and RSC, ANU: Protein Structure and Function, Osaka Univ.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Revisiting supersaturation as a factor determining amyloid fibrillation.2017

    • Author(s)
      Goto, Yuji
    • Organizer
      The 3rd Trilateral Workshop for Frontier Protein Studies
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Supersaturation-limited phase transition of denatured proteins producing amyloid fibrils.2017

    • Author(s)
      Goto, Yuji
    • Organizer
      The 5th APPA/12th PST joint conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 蛋白質の凝集と過飽和生命科学の開拓2017

    • Author(s)
      後藤祐児
    • Organizer
      長岡技術科学大学特別講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 蛋白質研究の歴史における凝集の位置づけと展望2017

    • Author(s)
      後藤祐児
    • Organizer
      蛋白研セミナー:産業応用を志向するタンパク質溶液研究
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Toward international cooperation in protein science.2017

    • Author(s)
      Yuji Goto
    • Organizer
      The 2020 PS/APPA/PSSJ Joint Symposium.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Revisiting supersaturation as a factor determining amyloid fibrillation2016

    • Author(s)
      Goto, Yuji
    • Organizer
      Third International Symposium on Protein Folding & Dynamics
    • Place of Presentation
      NCBS (Bangalore, India)
    • Year and Date
      2016-11-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アモルファス凝集とアミロイド線維の区別および疾患関連性2016

    • Author(s)
      後藤祐児
    • Organizer
      企業現場のニーズと先端蛋白質科学との接点を探るシンポジウム
    • Place of Presentation
      東京大学(東京都、文京区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 蛋白質の凝集と病気2016

    • Author(s)
      後藤祐児
    • Organizer
      大阪大学リサーチクラウドカフェ
    • Place of Presentation
      京阪電車なにわ橋駅(大阪府、大阪市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Toward understanding the unified mechanism of protein aggregation.2015

    • Author(s)
      後藤祐児
    • Organizer
      農芸化学会中部関西合同大会・シンポジウム:酵素活性分子研究の新展開-タンパク質のフォールディング研究と酵素機能の利用
    • Place of Presentation
      富山県立大学(富山県射水市)
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Supersaturation-limited protein misfolding revealed by ultrasonication.2015

    • Author(s)
      Goto, Yuji
    • Organizer
      IUBMB-SBBq Satellite Symposium: Frontiers in Protein Misfolding in Neurodegenerative Diseases and Cancer
    • Place of Presentation
      Rio de Janeiro (Brazil)
    • Year and Date
      2015-08-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Supersaturation-limited protein misfolding revealed by ultrasonication.2015

    • Author(s)
      Goto, Yuji
    • Organizer
      The 23rd International Union of Biochemistry and Molecular Biology (IUBMB) Congress
    • Place of Presentation
      Foz do Iguacu (Brazil)
    • Year and Date
      2015-08-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アミロイド線維形成における過飽和の果たす役割2015

    • Author(s)
      後藤祐児
    • Organizer
      第3回日本アミロイドーシス研究会学術集会:シンポジウム「アミロイド形成機構の解明と新たな治療戦略への展開」
    • Place of Presentation
      KKRホテル東京(東京都)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Supersaturation-limited and unlimited phase transitions compete to produce the pathway complexity in amyloid fibrillation.2015

    • Author(s)
      Goto, Yuji
    • Organizer
      SFB1035 Conference on Conformational Transitions in Proteins
    • Place of Presentation
      Venice (Italy)
    • Year and Date
      2015-05-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 大阪大学・蛋白質研究所・蛋白質構造形成研究室

    • URL

      http://www.protein.osaka-u.ac.jp/physical/yoeki.html

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Remarks] 大阪大学蛋白質研究所、蛋白質構造形成研究室

    • URL

      http://www.protein.osaka-u.ac.jp/laboratories/yoeki/

    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 超音波発生部材、超音波照射装置および超音波変性観察装置2017

    • Inventor(s)
      後藤祐児、荻博次 他
    • Industrial Property Rights Holder
      大阪大学、コロナ電気
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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