マラリア 寄生虫 の 輸入 糖 の 分子 基礎
Abdul Aziz Qureshi1, Albert Suades1, Rei Matsuoka1
1Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Nature
|January 31, 2020
まとめ
マラリア の 寄生虫
科学分野:
- 構造生物学
- 寄生虫学
- 生物化学
背景:
- 哺乳類のグルコーストランスポーター (GLUT) は専門です.
- プラズモディウム・ファルシパラムのヘキソストランスポーター1 (PfHT1) は,グルコースとフルクトースの両方を輸送する.
- PfHT1の砂糖の乱交性を理解することは,マラリア寄生虫の代謝に不可欠です.
研究 の 目的:
- PfHT1の結晶構造を決定する
- PfHT1の基質の乱交性の分子基礎を解明する.
- 糖結合と輸送ゲートとの結合メカニズムを理解する.
主な方法:
- D-グルコースと複合したPfHT1のX線結晶学
- PfHT1のサイト指向型変異
- 哺乳類のGLUTトランスポーターとの構造比較
主要な成果:
- PfHT1の糖結合部位は,GLUTトランスポーターと似ています.
- GLUT結合部位を模倣した変異は,PfHT1の糖質偏好を変化させなかった.
- PfHT1のTM7bヘリクスは,遮断された形状を採用し,基板ゲートダイナミクスを明らかにします.
- 糖結合とゲーティング間のアロステリック結合は,TM7bとTM1の間の極性接触を含みます.
結論:
- PfHT1は,変化した結合部位ではなく,進化した基質ゲートダイナミクスによって基質の乱交性を達成する.
- トランスメブランヘリクスの間の極性接触は,輸送に不可欠です.
- この研究は,マラリアの寄生虫の糖質輸送の 分子機構を提供する.
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