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人間のATR-ATRIPの同型である酵母 Mec1-Ddc2複合体の3.9 Å構造

  • 0Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Clinical Neuroscience (new York, N.y.) +

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2017年12月2日

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2017年12月2日

PubMedで要約を見る

まとめ

この要約は機械生成です。

アタキシア・テランジエクタシア変異およびRad3関連 (ATR) キナーゼ活性化メカニズムが明らかにされています. Cryo-EMは酵母ATR-ATRIP構造を示し,DNA損傷反応に不可欠なアロステリック活性化プロセスを明らかにします.

科学分野

  • 分子生物学
  • 構造生物学
  • 生物化学

背景

  • アタキシア・テランジエクタジア変異およびRad3関連 (ATR) キナーゼは,DNA損傷反応と複製ストレスに不可欠です.
  • ATRキナーゼ活性化の正確なメカニズムは,まだ十分に理解されていません.
  • ATRは,そのパートナーATR相互作用タンパク質 (ATRIP) と複合的に機能する.

研究 の 目的

  • ATR-ATRIPの活性化の構造的基礎を明らかにする.
  • ATRキナーゼの調節方法について 分子的な理解を提供するためです
  • Mec1-Ddc2複合体の構造を決定するために,ATR-ATRIPの酵母ホモログ.

主な方法

  • Mec1-Ddc2の構造を決定するために,冷凍電子顕微鏡 (cryo-EM) が使用されました.
  • 高解像度構造分析は3. 9アングストームで行われました.
  • 生物化学的測定は,規制領域を調査するために使用されました.

主要な成果

  • カタリシスの準備状態の整ったMec1-Ddc2の構造を決定した.
  • Mec1-Ddc2は,Mec1とDdc2の特定のドメインを含むヘテロダイマーを形成する.
  • Mec1のPRDドメインは活性化ループの阻害要素として特定され,アロステル活性化メカニズムを明らかにした.

結論

  • この研究は,ATR-ATRIP複合体の全体的なアーキテクチャを明確にします.
  • ATRキナーゼの調節と活性化を理解するための構造的枠組みが確立されています.
  • この研究は,DNA損傷反応キナーズのアロステリック制御に関する洞察を提供します.

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