Elucidation of the ion transport mechanism of the rotary molecular motor

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02409
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Chiba University
• Principal Investigator: Murata Takeshi 千葉大学, 大学院理学研究院, 教授 (80415322)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: V-ATPase / 分子モーター / 構造解析 / イオン輸送 / 分子メカニズム

Outline of Final Research Achievements

Enterococcal V-ATPase is a membrane protein that utilizes energy from ATP to transport Na+ while rotating, playing an essential role in the growth of enterococci. We discovered an inhibitor of V-ATPase and identified its potential as an antimicrobial agent against multidrug-resistant enterococci. In this study, we used cryo-electron microscopy to elucidate the detailed structure of the V-ATPase complex bound to the inhibitor. By integrating the obtained structural and functional analysis information, we clarified (i) the Na+ transport mechanism of this enzyme, (ii) the mechanism by which the inhibitor blocks Na+ transport, and (iii) the molecular differences between Na+ and H+ transport mechanisms. Currently, we are advancing the development of antimicrobial agents based on the obtained information.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

腸球菌V-ATPaseは、ATPのエネルギーを利用して回転しながらイオンを輸送する膜タンパク質であり、腸球菌の生育に重要な役割を果たしています。我々は、腸球菌V-ATPaseの阻害剤を発見し、多剤耐性腸球菌に対する抗菌薬としての可能性を見出しました。本研究では、阻害剤が結合した腸球菌V-ATPaseの詳細な立体構造を決定しました。そして、V-ATPaseがどのようにイオンを輸送するのか、阻害剤がどのようにV-ATPaseを阻害するのかを明らかにしました。現在、得られた情報を基に抗菌薬の開発を進めています。