C3bが因子B,Dと複合している構造は,補完コンバーターゼ形成の洞察を与えてくれる
Federico Forneris1, Daniel Ricklin, Jin Wu
1Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands.
Science (New York, N.Y.)
|January 6, 2011
まとめ
補完カスケードは,C3bと因子Bの分裂によって免疫反応を強める. 構造的な洞察は,C3bでタグ付けされた細胞への補完体増幅を標的として,この複合体をどのように因子Dが結合し活性化させるかを明らかにします.
科学分野:
- バイオケミストリー バイオケミストリー
- 免疫学 免疫学とは
- 構造生物学 構造生物学とは
背景:
- 補完カスケードは,先天的な免疫にとって不可欠であり,炎症と細胞クリアランスを媒介します.
- コンプリメント増幅はC3bB複合体に依存し,因子Dによって割れ,活性コンバータゼを形成する.
- この中心的なステップを理解することは,免疫反応の制御の鍵です.
研究 の 目的:
- コンプリメントプロコンバータゼC3bBとその複合体と因子Dの構造的基礎を解明する.
- C3bB複合体の因子D媒介の分裂と活性化のメカニズムを明らかにする.
- 補完体増幅がターゲット表面に限られていることを理解する.
主な方法:
- X線結晶学を用いて,C3bBの構造と,その複合体と因子Dの構造を決定した.
- 高解像度構造データ (4 Å,3.5 Å) が得られた.
- 構造分析は,タンパク質とタンパク質の相互作用と形状の変化に焦点を当てた.
主要な成果:
- プロコンバーターゼC3bBの結晶構造は4 Å解像度で決定されました.
- C3bB-因子D複合体の構造は3.5 Å解像度で解明されました.
- C3bbへの因子Bの結合は,C3bBのオープンで活性化可能な形状を誘導し,因子Dの結合と活性化を容易にします.
結論:
- 素因子Dは,触媒中心とは異なる素因子Bの開かれた形状のアロステリック部位に結合する.
- 基質によって引き起こされる形状の変化は,因子Dの抑制ループを移動させ,その活性化につながります.
- このコファクタに依存する基板誘発メカニズムは,補完体増幅がC3b-opsonized細胞に特異的に標的化されることを保証します.
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