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2023 Fiscal Year Final Research Report

Structure and mechanism of bacterial heme transporter

Research Project

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Project/Area Number 21H02421
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Sugimoto Hiroshi  国立研究開発法人理化学研究所, 放射光科学研究センター, 専任研究員 (90344043)

Co-Investigator(Kenkyū-buntansha) 木村 哲就  神戸大学, 理学研究科, 准教授 (70506906)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywordsクライオ電子顕微鏡 / ABCトランスポーター / ATP / 膜タンパク質
Outline of Final Research Achievements

Bacterial pathogens acquire the heme from host erythroid cell via several proteins and use it as a nutrition for their growth. The heme in the periplasm is imported into the cytoplasm across the inner membrane by heme transporter using ATP hydrolysis energy. In this study, we performed Cryo-EM analysis to obtain the structural snapshots of heme transporter from pathogenic bacteria which causes a serious respiratory disease to human. Our analysis revealed that the ATP-free apo structure has asymmetric TMD dimer with a narrow and closed cavity along the heme translocation channel. We suggest a possibility that apo-form of heme transporter might exist in equilibrium between two conformational states (asymmetric occluded structure and symmetric inward-facing structure) in physiological conditions. Furthermore, we compare the structures apo and ATP analog-bound form and propose a novel heme transporting mechanism based on these results.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はBurkholderia cenocepacia (セノセパシア菌)という日和見感染菌が持っているヘムトランスポーターを解析の対象としている。この細菌は指定難病である嚢胞生線維症という遺伝病患者の気管支や肺に感染しやすい細菌である。1990年代から多剤耐性菌の出現が臨床現場から報告されており、この患者はセノセパシア菌との戦いが大きな課題となっている。鉄の輸送や代謝に関わるタンパク質をターゲットとしたワクチン開発や治療薬の開発が試みられていることから、本研究で明らかにする構造情報は、創薬・医薬の基礎的な面で社会へ貢献する。

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Published: 2025-01-30  

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