2021 Fiscal Year Final Research Report
E. coli HdeA: Analysis of the reversible formation of fibrils by an environmentally responsive molecular chaperone
Project/Area Number |
19K06513
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 43020:Structural biochemistry-related
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Research Institution | Tottori University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 分子シャペロン / ペリプラズム / アミロイド線維 / 機能的変性構造 / フォールディング |
Outline of Final Research Achievements |
The molecular chaperones HdeA and HdeB utilize a unique mechanism where their acid denatured states are used to express molecular chaperone activity. In this study we demonstrate that both HdeA and HdeB form regular fibril structures resembling amyloid fibrils. HdeA and HdeB fibrils differ in one important aspect from typical fibrils; HdeA and HdeB fibrils formed in acid both dissolve at pH 7 to recover soluble protein. Our research involves elucidating the details of this reversible fibrillation of HdeA and HdeB at acidic pH, with special focus on the numerous experimental conditions that alter the original reversibility of the fibrillation. We found multiple conditions under which both HdeA and HdeB form alternative fibrils that are not dissolved at pH 7, and the details of our experiments provide insights in understanding protein denaturation and fibrillation, as well as the mechanisms underlying the activities of intrinsically denatured proteins.
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Free Research Field |
構造生物化学
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Academic Significance and Societal Importance of the Research Achievements |
「蛋白質のダイナミックな変性構造が機能実現と調節に活用される」現象は最近注目を浴びている。特に真核細胞内で顕著に見られるこの変性蛋白質の新たな役割であるが,研究のモデルとなるような,蛋白質の変性構造と機能が関連付けられている蛋白質、特に,詳細な物理化学的解析に適したモデルとなる様な蛋白質の例がまだ少ない。本研究のHdeAとHdeBは「機能的変性蛋白質」の好例であり,更に「蛋白質の変性疾患」や「分子シャペロン」という重要現象とも関連性が高い。この為,本研究で得られた知見は広く他の蛋白質において「変性構造の役割」を理解する為に役立つ普遍的なものとなる。
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