病気に関連したプリオンタンパク質がプラズミノゲンと結合する
M B Fischer1, C Roeckl, P Parizek
1Institute for Neuropatholgy, University Hospital of Zurich, Switzerland.
Nature
|December 2, 2000
まとめ
研究者らは,血中のプラズミノゲンを特定し,病気に関連したプリオンタンパク質 (PrPSc) に結合するが,通常のプリオンタンパク質 (PrPC) に結合しない. この発見は,伝染性スポンジ状脳症の診断に役立つかもしれない.
科学分野:
- 神経科学は神経科学である.
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
背景:
- 伝染性スポンジ状脳症 (TSEs) は,異常なプリオンタンパク質 (PrPSc) の蓄積と関連しており,これは細胞プリオンタンパク質 (PrPC) の誤折り形である.
- PrPSc複製のメカニズムと,神経病理を引き起こすための細胞成分との相互作用は,まだ完全に理解されていません.
- 形状に基づいてPrPCとPrPScを区別することは,大きな課題でした.
研究 の 目的:
- PrPCとPrPScを区別できる血液内の内生因子を特定する.
- プリオン病の病原性および潜在的な診断用途におけるそのような要因の役割を調査する.
主な方法:
- 人間とマウスの血液をスクリーニングして,PrPScを結合させる活動があるが,PrPCは結合しない.
- この結合活動に責任を負う特定のタンパク質を特定する.
- 結合相互作用の特徴づけは,デナチュラントによる干渉や競争研究を含む生化学的測定を用いて行われます.
主要な成果:
- 血中のプロプロテアゼであるプラズミノゲンを,PrPScとプリオン感染性を結合するタンパク質として識別したが,PrPCは検出されなかった.
- プラズミノゲンへのPrPSc結合は形状に依存しており,6M尿素またはグアニジンによって廃止されていることが実証されました.
- プラズミノゲンのライシン結合部位1 (kringles I-III) が,この特定の結合を媒介し,ライシンと競合できることを示した.
結論:
- プラズミノゲンは,正常なPrPCよりも病的なPrPScコンフォマーを選択的に結合する最初の内生因子です.
- プラズミノゲンのこのユニークな結合特性により,TSEの診断ツールを開発するための潜在的な道が開かれている.
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