ミコバクテリアのABCトランスポーターは,水性化合物の吸収を媒介する
S Rempel1,2, C Gati3,4, M Nijland1
1Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
Nature
|April 17, 2020
まとめ
Mycobacterium tuberculosisは,そのエクスポーター構造にもかかわらず,ビタミンB12 (コバラミン) を輸送するためにRv1819cを使用しています. この発見は,Rv1819cが結核の病原化に不可欠な多溶質トランスポーターであることを明らかにしています.
科学分野:
- 微生物学
- 構造生物学
- 生物化学
背景:
- Mycobacterium tuberculosis (Mtb) は結核を引き起こし,ビタミンB12 (コバラミン) を合成することができるが,コバラミンの摂取は病原性に関連している.
- Mtbには特徴的なコバラミントランスポーターがないが,Rv1819cは,ATP結合カセット (ABC) エクスポーターフォールドが予測されているにもかかわらず,コバラミン吸収に不可欠である.
研究 の 目的:
- Mycobacterium tuberculosisにおけるRv1819cタンパク質の構造と機能を明らかにする.
- コバラミン輸送におけるRv1819cの役割と,ABCの輸出者としての構造的予測に関する矛盾する証拠を調和させる.
主な方法:
- Rv1819cの3D構造を決定するX線結晶学.
- Rv1819cアミノ酸配列と構造特性のバイオ情報分析
- コバラミンとブレオミシンに対するRv1819cの輸送能力を評価する機能検査
主要な成果:
- 構造はRv1819cがABCエクスポーターフォールドを持っていることを確認します.
- Rv1819cの内部で,輸送を容易にする大きな,水で満たされた空洞 (7,700 Å3) が確認された.
- Rv1819cは,構造的に異なる水性化合物であるコバラミンとブレオミシンの両方を輸送する能力を示した.
結論:
- Rv1819cは,水性分子のための多溶質トランスポーターとして機能します.
- このトランスポーターは,ABCトランスポーターファミリーのマルチドラッグエクスポーターに類似しています.
- Rv1819cの二重輸送能力は,結核の病原性と潜在的な治療戦略の理解に意味を持っています.
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