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Study on the thermodynamics and regulation of amyloid formation using calorimetry

Research Project

Project/Area Number 17K07362
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biophysics
Research InstitutionOsaka University

Principal Investigator

李 映昊  大阪大学, たんぱく質研究所, 講師 (70589431)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Discontinued (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsAmyloid fibril / Calorimetry / Energy landscape / Kinetics / Thermodynamics / Protein aggregation / Protein misfolding / Misfolding and disease / Amyloid
Outline of Annual Research Achievements

In order to study thermodynamics of protein misfolding-induced aggregation and establish a new assay, isothermal titration calorimetry (ITC) was performed on amyloidogenesis of several amyloidogenic proteins and peptides. I revealed that amyloid formation resulited in exothermic heat after the lag time, and obtained thermodynamic parameters such as the change in enthalpy using in-house algorithms. I further challenged to elucidate the kinetic property of amyloid formation, and could calculate the rate constant of nucleation and elongation of amyloid fibrillation. Energy landscape built using these parameters revealed the polymorphic amyloidogenesis of b2m.ITC-based assay provides a powerful method for the study of the thermodynamics, kinetics, and mechanism of protein aggregation.

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 11 results)

  • [Journal Article] Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease2018

    • Author(s)
      Kim Donghoon、Yoo Je Min、Hwang Heehong、Lee Junghee、Lee Su Hyun、Yun Seung Pil、Park Myung Jin、Lee MinJun、Choi Seulah、Kwon Sang Ho、Lee Saebom、Kwon Seung-Hwan、Kim Sangjune、Park Yong Joo、Kinoshita Misaki、Lee Young-Ho、Shin Seokmin、Paik Seung R.、Lee Sung Joong、Lee Seulki、Hong Byung Hee、Ko Han Seok
    • Journal Title

      Nature Nanotechnology

      Volume: - Issue: 9 Pages: 812-818

    • DOI

      10.1038/s41565-018-0179-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stability and subunit assembly of nylon hydrolase: structural basis of correct subunit assembly, aggregation, and intracellular degradation of the precursor protein2018

    • Author(s)
      Seiji Negoro, Naoki Shibata, Young-Ho Lee, Ikki Takehara, Ryo Kinugasa, Keisuke Nagai, Yusuke Tanaka, Dai-ichiro Kato, Masahiro Takeo, Yuji Goto and Yoshiki Higuchi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 9725-9725

    • DOI

      10.1038/s41598-018-27860-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Energy landscape of polymorphic amyloid generation of β2-microglobulin revealed by calorimetry.2018

    • Author(s)
      Kinoshita M., Lin Y., Itoh D., Okumura M., Markova N., Ladbury J.E., Sterpone F., and Lee Y.H.*
    • Journal Title

      Chem Commun (Camb).

      Volume: 57 Issue: 57 Pages: 7995-7998

    • DOI

      10.1039/c8cc02718h

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra.2018

    • Author(s)
      Micsonai, A., Wien, F., Bulyáki, E., Kun, J., Moussong, E., Lee, Y.-H., Goto, Y., Réfrégiers, M., Kardos, J.
    • Journal Title

      Nucleic Acids Research

      Volume: 46 (W1) Issue: W1 Pages: 315-322

    • DOI

      10.1093/nar/gky497

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of membrane curvature on amyloid aggregation2018

    • Author(s)
      Terakawa Mayu S.、Lin Yuxi、Kinoshita Misaki、Kanemura Shingo、Itoh Dai、Sugiki Toshihiko、Okumura Masaki、Ramamoorthy Ayyalusamy、Lee Young-Ho
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: - Issue: 9 Pages: 30130-30135

    • DOI

      10.1016/j.bbamem.2018.04.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Semen-derived amyloidogenic peptides-Key players of HIV infection2018

    • Author(s)
      Lee Young-Ho、Ramamoorthy Ayyalusamy
    • Journal Title

      Protein Science

      Volume: - Issue: 7 Pages: 1151-1165

    • DOI

      10.1002/pro.3395

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Membrane-induced initial structure of α-synuclein control its amyloidogenesis on model membranes2018

    • Author(s)
      Terakawa Mayu S.、Lee Young-Ho、Kinoshita Misaki、Lin Yuxi、Sugiki Toshihiko、Fukui Naoya、Ikenoue Tatsuya、Kawata Yasushi、Goto Yuji
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1860 Issue: 3 Pages: 757-766

    • DOI

      10.1016/j.bbamem.2017.12.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides2017

    • Author(s)
      Kinoshita Misaki、Kakimoto Erina、Terakawa Mayu S.、Lin Yuxi、Ikenoue Tatsuya、So Masatomo、Sugiki Toshihiko、Ramamoorthy Ayyalusamy、Goto Yuji、Lee Young-Ho
    • Journal Title

      Physical Chemistry Chemical Physics

      Volume: 19 Issue: 24 Pages: 16257-16266

    • DOI

      10.1039/c6cp07774a

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kinetics and polymorphs of yeast prion Sup35NM amyloidogenesis2017

    • Author(s)
      Kinoshita Misaki、Lin Yuxi、Nakatsuji Masatoshi、Inui Takashi、Lee Young-Ho
    • Journal Title

      International Journal of Biological Macromolecules

      Volume: 102 Pages: 1241-1249

    • DOI

      10.1016/j.ijbiomac.2017.05.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] ITCによる分子間相互作用の解析2018

    • Author(s)
      Lee Young-Ho
    • Organizer
      大阪大学蛋白質研究所バイオマテリアル評価セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 1.Microscopic and macroscopic understanding of disease-causing protein misfolding and aggregation2018

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at Yonsei University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 2.Simple and Informative NMR and ITC Application to the Study on Protein Folding, Misfolding, and Interaction2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at Yonsei University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Thermodynamics of protein misfolding and aggregation2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Samsung Global Research Symposium on Structure, Dynamics, and Thermodynamics of Biomolecular Networks
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Delicate interprotein interactions control the onset of Parkinson's disease and apoptosis2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      The 8th KRIBB ASIA-PACIFIC IDP SYMPOSIUM
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Thermodynamics of protein misfolding and aggregation2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at Kanazawa University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Protein misfolding and aggregation for neurodegenerative diseases and amyloidosis2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at the Institute of Multidisciplinary Research for Advanced Materials of Tohoku University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Lessons from the recent studies on protein aggregation for neurodegenerative diseases and amyloidosis2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      The Annual Meeting of Japanese Photochemistry, September 4-6, 2017, Tohoku University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] New approaches for the diagnosis and treatment of protein misfolding diseases2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Symposium on Biophysical approach on disease-related proteins toward application for medical and pharmaceutical sciences, the 55th Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Thermodynamics of protein misfolding and aggregation2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      International Symposium on Protein Misfolding Diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 10.Simple and Informative NMR Application to the Study on Protein Folding, Misfolding, and Interaction2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      The Annual Meeting of Korean Magnetic Resonance Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 11.Thermodynamics and calorimetry on the biological system and disease-related protein aggregation2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at Konkuk University
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Thermodynamic study on interprotein interactions using isothermal titration calorimetry2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      The 17th Annual Meeting of the Protein Science Society of Japan (Invited luncheon seminar)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Biocalorimetric approach for the study on disease-related protein misfolding and aggregation2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Malvern webinar
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Understanding of misled protein behavior and its control2017

    • Author(s)
      Lee Young-Ho
    • Organizer
      Invited seminar at Sookmyung Women's University
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2019-12-27  

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