Elucidation of a novel mechanism for repairing oxidized proteins in the bacterial periplasmic space

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K05388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38020:Applied microbiology-related
• Research Institution: Shinshu University
• Principal Investigator: OGASAWARA Hiroshi 信州大学, 学術研究院総合人間科学系, 准教授 (30535232)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: Escherichia coli / Two-component system / HprS/HprR / ROS / Periplasmic space

Outline of Final Research Achievements

Proteins located in the periplasmic space near by the outermembrane of bacteria are likely to be exposed to reactive oxygen species in the environment and frequently undergoing oxidative damage. Most of the repair mechanisms for oxidized proteins that have been identified and elucidated so far work mainly in the cytoplasm, and the mechanism in the periplasmic space has remained unclear. In this study, we aimed to clarify the molecular mechanisms involved in the activation of HprS, which functions as a sensor for the reactive oxygen species in the periplasmic space of bacteria, and the role of HprS homologues in Gram-negative bacteria.

Free Research Field

農学

Academic Significance and Societal Importance of the Research Achievements

本研究は、細菌のペリプラズム空間における酸化的損傷タンパク質の修復機構とその発現誘導の分子メカニズムの解明が主な目的である。これまで細菌ペリプラズム空間で機能するプロテアーゼやシャペロンタンパク質は知られているが、酸化的損傷タンパク質の修復機構は、殆ど不明であった。本研究で機能解析を進めたセンサーキナーゼHprSとその制御下にあるメチオニンスルホキシド還元酵素MsrQPは、グラム陰性細菌に広く保存され、これらは細胞外ROSに対する耐性能付与に重要な役割を果たしていると考えられるため、病原性大腸菌を始めとする多くのグラム陰性細菌の新たな創薬ターゲットとしての可能性も期待できる。