転写活性化剤BmrRの結晶構造は,DNAと薬物に結合している
1Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Nature
|February 24, 2001
まとめ
バクテリアの多剤耐性症は,しばしば薬物の放出ポンプによって引き起こされます. この研究では,BmrR (転写レギュレータ) が,抵抗を制御する新しいメカニズムであるDNA塩基対の断裂とスライドによってトランスポーター遺伝子発現を活性化する方法が明らかにされています.
科学分野:
- 分子生物学は分子生物学である.
- 微生物学 微生物学とは
- 構造生物学 構造生物学とは
背景:
- バクテリアの多剤耐性 (MDR) は重要な臨床的課題であり,しばしば膜を横断する薬物流出媒介によって媒介される.
- これらのトランスポーターの発現は,Bacillus subtilisのBmrRのような有毒化合物と結合する転写因子によって頻繁に調節されます.
研究 の 目的:
- MerRファミリーの転写調節体BmrRが,薬物結合に反応して,多剤輸送遺伝子 (bmr) の転写を活性化する構造的メカニズムを解明する.
- プロモーター再構成を含む転写活性化の分子基盤を理解する.
主な方法:
- X線結晶学を用いて,BmrR.の3.0 Å解像度構造を決定した.
- 構造は,薬物テトラフェニルフォスフォニウム (TPP) とBMRプロモーター配列を含むDNAオリゴデオキシヌクレオチドで複合的に決定されました.
主要な成果:
- 結晶構造は,BmrRがTPPとBMRプロモーターDNAに結合していることを示しています.
- 局所的なDNA塩基対の破壊,スライディング,および -35および -10プロモーター要素の再調整を含む,予期せぬ転写活性化メカニズムが観察されました.
- この再構成は,RNAポリメラーゼとの生産的な相互作用を容易にする.
結論:
- BmrRは,毒性化合物の暴露と戦うためにDNAの構造的再編成を含む特異的な転写活性化メカニズムを使用しています.
- このメカニズムを理解することで,細菌の多剤耐性や治療的介入の潜在的な標的についての洞察が得られます.
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