Research on the interaction mechanisms between Stomatin-like proteins and ion channel proteins

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15732
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Osaka University
• Principal Investigator: TAKEKAWA Norihiro 大阪大学, 大学院理学研究科, 助教 (50791810)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ストマチン / チャネル / 細菌 / べん毛 / 蛋白質間相互作用

Outline of Final Research Achievements

This study aimed to elucidate the interaction mechanism between slipin proteins and their corresponding channel proteins using molecular structural analysis. The complex of different slipin proteins and their respective channel proteins were examined by using nematodes and bacteria as models. The expression system of full-length proteins and fragments were established, and the identification of stable and purifiable fragments was successful. The propensity of some proteins to form multimeric structures was also consistently confirmed. Weak interactions between MEC-2 and MEC-4 were detected. The structure of MotA/B homologs was revealed by cryo-electron microscopy, and the mechanism of structural changes in MotB homologs through binding to Na+ was also elucidated.

Free Research Field

生物学

Academic Significance and Societal Importance of the Research Achievements

ほとんど全ての生物に保存されているslipinは、多様な機能を持つチャネル/トランスポータータンパク質を制御する。しかし、異なる構造を持つチャネルタンパク質をどのように制御するのか、また、同じ構造モチーフを持つslipinがどのように機能的な多様性を生み出すのかが興味深い。さらに、チャネルやトランスポーターは生物活動に必須であり、slipinは病理学的にも重要なターゲットである。本研究は、病理学的な原因追求や新規薬剤の探索に繋がる可能性がある。同一ファミリーのタンパク質がここまで多様な相互作用パートナーを持つ例はほとんどなく、今後も生命現象の根幹に関わる重要な課題である。