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2023 Fiscal Year Final Research Report

Elucidation of driving forces underlying protein folding coupled with ligand binding.

Research Project

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Project/Area Number 20K06578
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43040:Biophysics-related
Research InstitutionNagoya University

Principal Investigator

Kosuke Maki  名古屋大学, 理学研究科, 准教授 (30361570)

Project Period (FY) 2020-04-01 – 2024-03-31
Keywords蛋白質 / フォールディング / 複合体 / スタフィロコッカル・ヌクレアーゼ
Outline of Final Research Achievements

By regulating solution conditions, we have shown that addition of a specific ligand, protein folding can be induced. We applied the method to the folding of a model protein, staphylococal nuclease (SNase). A series of spectroscopic probs including NMR were used to follow the folding reaction. In addition to those methods, replica-permutation molecular dynamics simulation and a statistical mechanical model were used to characterize the structural properties and energetics of the relevant species. Furthermore, we exploited a chemically modified ligand to investigate roles of each phosphorylation groups of the ligand.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

蛋白質が構造変化を伴い複合体を形成する際に、リガンド結合と構造変化が起こる順序を調べた。広い範囲にわたる実験・計算機シミュレーションによる結果を踏まえて、モデル計算に基づいて、リガンド濃度に依存して反応経路が変化していくことが明らかになった。蛋白質複合体形成は神経変性疾患などと深い関連があることから、本研究の結果は蛋白質科学のみならず医学にも貢献し得るものである。

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Published: 2025-01-30  

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