ヒトPCNAと複合したp21 ((WAF1/CIP1) のC端末領域の構造
J M Gulbis1, Z Kelman, J Hurwitz
1Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Cell
|October 18, 1996
まとめ
結晶構造は,細胞サイクルタンパク質p21 (WAF1/CIP1) が,DNAポリメラーゼデルタプロシシビティ因子PCNA (増殖細胞核抗原) を抑制する方法を示しています. この相互作用は,p21がPCNAとベータシートを形成し,他のポリメラーゼ成分をブロックする可能性が高い.
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- 増殖細胞核抗原 (PCNA) は,DNAポリメラーゼデルタプロセシビティの決定的な要因である.
- 細胞サイクルチェックポイントタンパク質p21 (WAF1/CIP1) は,PCNA機能を抑制することが知られている.
- この阻害の分子基礎を理解することは,細胞サイクル調節とDNA複製を理解する鍵です.
研究 の 目的:
- 人間のPCNA-p21複合体の高解像度結晶構造を決定するために.
- PCNAとp21ペプチドの間の分子相互作用を解明する.
- p21がPCNA活動を抑制するメカニズムについての洞察を提供するためです.
主な方法:
- 構造を決定するために,X線結晶学を用いた.
- 構造は2.6アングストームの解像度で解像しました.
- 相互作用と阻害メカニズムを確認するために生化学的測定を用いた.
主要な成果:
- PCNA-p21複合体の結晶構造が成功裏に決定されました.
- p21は1:1のステキオメトリック比でPCNAと結合する.
- 重要な相互作用は,p21がPCNAインタードメインコネクタループとベータシートを形成し,トリメアリング構造を維持することを含む.
- PCNAリング内の中央の穴は,DNA相互作用のためにアクセス可能である.
結論:
- p21ペプチドはPCNAに広く結合し,ベータシート相互作用を形成します.
- PCNAのトリメアリング構造は,p21結合時に保存されます.
- p21は,直接DNAの相互作用を阻害するのではなく,他のポリメラーゼアセンブリ成分の結合をステリックに阻害することによってPCNAを抑制する可能性が高い.
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