Functional analysis of translocon factors involved in the topogenesis of membrane proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: University of Hyogo
• Principal Investigator: SAKAGUCHI Masao 兵庫県立大学, 理学研究科, 教授 (30205736)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: タンパク質膜透過

Outline of Final Research Achievements

Membrane proteins have many essential roles in cells. We analyzed the novel functions of endoplasmic reticulum translocon involved in their three-dimensional structure formation. The translocon channel has been shown to have a novel functional site that accepts moderate hydrophobic sequences. The site of action was identified by systematic chemical crosslinking. By exploiting newly developed probes, we have found novel genes related to membrane translocation and integration of proteins. We also discovered a novel concept that multifunctional chaperones in the lumen of the endoplasmic reticulum contribute to synthesis-coupled protein translocation.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

内在性膜タンパク質は細胞の生命維持に必須であり、その構造形成過程の理解は生命活動の理解や、医学薬学農学領域の応用分野の基盤として重要である。この過程は、タンパク質の構造形成にはその配列特性のみで十分であるとするアンフィンゼンドグマに反し、構造規定因子が決定的に重要であることを示した。本研究で解明された新規知見は、膜タンパク質構造形成の新しい側面を解明すると同時に、新規機能性膜タンパク質のデザインや、疾病の新規病因解明につながると期待される。