2022 Fiscal Year Final Research Report

Structural basis for recognition and regulation of protein folding intermediate by molecular chaperones in the endoplasmic reticulum

Research Project

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Project/Area Number	20KK0156
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research Institution	The University of Tokushima
Principal Investigator	SAIO Tomohide 徳島大学, 先端酵素学研究所, 教授 (80740802)
Co-Investigator(Kenkyū-buntansha)	奥村正樹東北大学, 学際科学フロンティア研究所, 准教授 (50635810) 金村進吾関西学院大学, 理学部, 助教 (50803178)
Project Period (FY)	2020-10-27 – 2023-03-31
Keywords	タンパク質フォールディング / シャペロン / 小胞体
Outline of Final Research Achievements	Chaperones play a crucial role in maintaining protein homeostasis in the cell, making them an intriguing target for the treatment and prevention of neurodegenerative diseases. However, the mechanisms for the regulation of protein folding by molecular chaperones remain largely elusive. Of particular interest is understanding the functions of the chaperones in endoplasmic reticulum (ER) that is responsible for the maturation of a number of newly synthesized proteins. In this study, we conducted international collaborative research that focused on ER chaperones. Leveraging cutting-edge structural analysis techniques utilizing paramagnetic probes and oxidative folding analysis in ER, we tried to unravel the structural basis for recognition and regulation of folding intermediates by molecular chaperones.
Free Research Field	構造生物学
Academic Significance and Societal Importance of the Research Achievements	超高齢化が一段と進む我が国において、神経変性疾患などの加齢性疾患の予防法・治療法開発への社会的ニーズは一層高まっている。神経変性疾患においては、タンパク質の品質管理機構が乱れ、タンパク質凝集体やアミロイド線維などが沈着する。神経変性疾患の予防法・治療法開発のための基盤として、タンパク質品質管理の分子レベルでのメカニズム解明が待ち望まれている。本研究は、細胞内タンパク質の品質管理において中心的役割を担うシャペロンに着目し、タンパク質品質管理のメカニズム解明に取り組んだ点に、高い社会的意義を有する。