Application of molecular shielding effect of intrinsically disordered proteins towards development of protein stabilizers

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14707
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biophysics
• Research Institution: Nagoya University
• Principal Investigator: HIROAKI Hidekazu 名古屋大学, 創薬科学研究科, 教授 (10336589)
• Co-Investigator(Renkei-kenkyūsha): IKURA Teikichi 東京医科歯科大, 難治疾患研究所, 准教授 (50251393) ; HAMADA Daizo 神戸大学, 大学院工学研究科, 特命准教授 (60372132)
• Research Collaborator: TENNO Natsuko
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 分子シールド効果 / 分子夾雑 / 高分子クラウディング / 朝倉・大沢理論 / 天然変性タンパク質 / アミロイド線維

Outline of Final Research Achievements

Macromolecular crowding is the phenomenone that alters the properties of molecules in a solution when high concentrations of macromolecules (molecular crowders) are present. In a living cell, one of the most abundant molecular crowders is the protein itself. We focus on the properties of the intrinsically disordered proteins (IDPs) as a macromolecular crowder. We recently found that IDPs have cryoprotective activity against the other proteins, and we hypothesized that this cryoprotective activity was origined by IDP's molecular shileding effect. For further understanding IDP's molecular shielding effect, aggregation inhibition of IDPs in the other conditions were examined. We found that some IDPs can suppress amyloid formation of Abeta(1-42) peptide.
We have also succeeded in developing the new method to discriminate IDPs from non-IDPs using NMR signal. In detail, chemical shift temperature coefficient (CSTC) of amide protons is a good indication.

Free Research Field

生物物理学