Analysis on the design principle of proteins with intrinsic sequence variations
| Project/Area Number |
26440076
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Kobe University (2015-2016)
Mie University (2014) |
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Principal Investigator |
Daizo Hamada 神戸大学, 工学研究科, 特命准教授 (60372132)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 抗体 / ALアミロイドーシス / フォールディング / 複合体形成 / 重水素交換 / 蛋白質間相互作用 / 蛋白質の安定性 / アミロイド / アミロイド線維 / φ値解析 / 水素・重水素交換 / X線結晶構造解析 / NMR / タンパク質のフォールディング / エネルギー地形 / 平衡論 / 速度論 |
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| Outline of Final Research Achievements |
Here, we analysed the folding mechanism of immunoglobulin light chain variable domain (VL) which intrinsically have sequence variation, although folded into the same structure. We performed various thermodynamic, kinetic and structural analyses on the monomeric VL that we invented ourselves in another study and clarified the core region for folding of VL. We also found the unexpected heat-induce dimerization for original VL, which instinctively against general idea that dimeric proteins have to dissociate into monomers by heating. We clarified the mechanism of this heat-induce dimerization by a series of thermodynamic analysis. These pieces of information about the folding of VL will be applicable to improve the thermal stability of proteins used in various fields and also provided a significant insight into the development of strategy for prevention, diagnostics and treatment against AL amyloidosis which the amyloid formation by immunoglobulin light chain is associated with.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Identification and characterization of PKCγ, a kinase associated with SCA14, as an amyloidogenic protein.2015
Author(s)
Takahashi H, Adachi N, Shirafuji T, Danno S, Ueyama T, Vendruscolo M, Shuvaev AN, Sugimoto T, Seki T, Hamada D, Irie K, Hirai H, Sakai N, *Saito N.
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Journal Title
Hum Mol Genet.
Volume: 24
Issue: 2
Pages: 525-539
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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