Mechanism and regulation of protein aggregation in complicated cellular systems

• Project/Area Number: 15H04362
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: Osaka 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: ¥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.

Research Products

• [Int'l Joint Research] エトバッシュローランド大学(ハンガリー)
• [Int'l Joint Research] ユニバーシティ・カレッジ・ロンドン(英国)
• [Int'l Joint Research] ウディネ大学/パビア大学(イタリア)
• [Int'l Joint Research] ミュンヘン工科大学(ドイツ)
• [Int'l Joint Research] オーストラリア国立大学(オーストラリア)
• [Int'l Joint Research]
• [Int'l Joint Research] エトバッシュローランド大学(ハンガリー)
• [Int'l Joint Research] ユニバーシティ・カレッジ・ロンドン(英国)
• [Int'l Joint Research] ウディネ大学/パビア大学(イタリア)
• [Int'l Joint Research] Eotvos Lorand University(ハンガリー)
• [Int'l Joint Research] Australian National University(オーストラリア)
• [Int'l Joint Research] Technische Universitat Munchen(ドイツ)
• [Journal Article] A new look at an old view of denaturant induced protein unfolding (2018)
  • 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
  • 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-lactoglobulin (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Nanoscale Dynamics of Protein Assembly Networks in Supersaturated Solutions (2017)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation (2017)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Salt-induced formations of partially folded intermediates and amyloid fibrils suggests a common underlying mechanism (2017)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Drastic acceleration of fibrillation of insulin by transient cavitation bubble (2017)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 Patients (2015)
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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
  • Invited
• [Presentation] Toward international cooperation in protein science. (2017)
  • Author(s): Yuji Goto
  • Organizer: The 2020 PS/APPA/PSSJ Joint Symposium.
  • Invited
• [Presentation] Revisiting supersaturation as a factor determining amyloid fibrillation (2016)
  • Author(s): Goto, Yuji
  • Organizer: Third International Symposium on Protein Folding & Dynamics
  • Place of Presentation: NCBS (Bangalore, India)
  • Year and Date: 2016-11-08
  • 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）
  • 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）
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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/
• [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