Study on the thermodynamics and regulation of amyloid formation using calorimetry

利用量热法研究淀粉样蛋白形成的热力学和调控

• 批准号: 17K07362
• 负责人: 李 映昊
• 金额: $ 3.16万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2017
• 资助国家: 日本
• 起止时间: 2017-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K07362/
• 关键词: Amyloid fibril; Calorimetry; Energy landscape; Kinetics; Thermodynamics; Protein aggregation; Protein misfolding; Misfolding and disease; Amyloid

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.

为了研究蛋白质错误折叠诱导聚集的热力学并建立一种新的分析方法，采用等温滴定量热法（ITC）对几种淀粉样蛋白和多肽的淀粉样形成进行了研究。我揭示了淀粉样蛋白的形成在滞后时间后会产生放热，并使用内部算法获得了热力学参数，如焓变。我进一步挑战阐明淀粉样蛋白形成的动力学性质，并可以计算淀粉样蛋白纤颤成核和延伸的速率常数。利用这些参数构建的能量格局揭示了b2m的多态淀粉样蛋白形成。基于itc的分析为研究蛋白质聚集的热力学、动力学和机制提供了一种强有力的方法。

项目成果

Lessons from the recent studies on protein aggregation for neurodegenerative diseases and amyloidosis.

最近关于神经退行性疾病和淀粉样变性蛋白质聚集的研究的教训。

• 发表时间: 2017
• 作者: 牟田 寛弥; 宗 正智; 櫻井 一正; 後藤 祐児;李映昊;李映昊;李映昊;李映昊;李映昊
• 通讯作者: 李映昊

Biocalorimetric approach for the study on disease-related protein misfolding and aggregation

用于研究疾病相关蛋白质错误折叠和聚集的生物量热方法

• 发表时间: 2017
• 作者: Kinoshita Misaki;Lin Yuxi;Nakatsuji Masatoshi;Inui Takashi;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho
• 通讯作者: Lee Young-Ho

1.Microscopic and macroscopic understanding of disease-causing protein misfolding and aggregation

1.对致病蛋白质错误折叠和聚集的微观和宏观理解

• 发表时间: 2018
• 作者: Kinoshita Misaki;Lin Yuxi;Nakatsuji Masatoshi;Inui Takashi;Lee Young-Ho;Lee Young-Ho;Lee Young-Ho
• 通讯作者: Lee Young-Ho

Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides

• DOI: 10.1039/c6cp07774a
• 发表时间: 2017-06-28
• 期刊: PHYSICAL CHEMISTRY CHEMICAL PHYSICS
• 影响因子: 3.3
• 作者: Kinoshita, Misaki;Kakimoto, Erina;Lee, Young-Ho
• 通讯作者: Lee, Young-Ho

Kinetics and polymorphs of yeast prion Sup35NM amyloidogenesis

酵母朊病毒Sup35NM淀粉样变的动力学和多态性

• DOI: 10.1016/j.ijbiomac.2017.05.001
• 发表时间: 2017
• 期刊: International Journal of Biological Macromolecules
• 影响因子: 8.2
• 作者: Kinoshita Misaki;Lin Yuxi;Nakatsuji Masatoshi;Inui Takashi;Lee Young-Ho
• 通讯作者: Lee Young-Ho