Study on the thermodynamics and regulation of amyloid formation using calorimetry

2018 Fiscal Year Annual Research Report

• Project/Area Number: 17K07362
• Research Institution: Osaka 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
• Keywords: Amyloid fibril / Calorimetry / Energy landscape / Kinetics / Thermodynamics / Protein aggregation / Protein misfolding / Misfolding and disease

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.

Research Products

• [Journal Article] Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease (2018)
  • 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: - Pages: -
  • DOI: 10.1038/s41565-018-0179-y
  • 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 protein (2018)
  • 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 Pages: 9725
  • DOI: 10.1038/s41598-018-27860-w
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Energy landscape of polymorphic amyloid generation of β2-microglobulin revealed by calorimetry (2018)
  • Author(s): Misaki Kinoshita, Yuxi Lin, Itoh Dai, Masaki Okumura, Natalia Markova, John E. Ladbury, Fabio Sterpone and Young-Ho Lee
  • Journal Title: Chemical Communications Volume: 54 Pages: 7995-7998
  • DOI: 10.1039/c8cc02718h
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] BeStSel: a webserver for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra (2018)
  • Author(s): Andras Micsonai, Frank Wien, Eva Bulyaki, Judit Kun, Eva Moussong, Young-Ho Lee, Yuji Goto, Matthieu Refregiers, Jozsef Kardos
  • Journal Title: Nucleic Acids Research Volume: 46 Pages: 315-322
  • DOI: 10.1093/nar/gky497
  • Peer Reviewed / Int'l Joint Research
• [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
  • Invited