3つの酵母プリオン株のタンパク質のみの伝播

Chih-Yen King¹, Ruben Diaz-Avalos

¹Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA. chihyen@sb.fsu.edu

Nature

|March 19, 2004

まとめ

この研究は,酵母モデルを使用して,プリオン菌株はタンパク質のみであることを示しています. 同じタンパク質の異なる折り畳みパターンは,異なるプリオン菌株情報をコードし,感染性を伝播します.

科学分野:

バイオケミストリーバイオケミストリー
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

背景:

プリオンは,神経変性疾患に関与する感染性タンパク質です.
単一のタンパク質から異なるプリオン菌株がどのように発生するか,そしてそれらの基本的な組成について,重要な疑問が残っています.
イースト [PSI] の遺伝子要素であるモデルプリオンが,ナンセンス変異の読み通しを強化する.

研究の目的:

プリオン菌株のタンパク質のみの性質を調査するために.
同じタンパク質の異なる折り畳みパターンによって異なるプリオン株がコードされているかどうかを判断する.
プリオン感染性の新たな生成を in vitro で実証する.

主な方法:

イーストのSup35プリオンタンパク質の感染性繊維の集積物の浄化.
精製された集積物を種として使用して,長さのあるアミロイド繊維のインビトロ生成.
電子顕微鏡と電子 difraktionで繊維構造を分析する.
感染性を評価するために,酵母宿主にin vitroで生成された繊維を導入する.

主要な成果:

感染性アミロイド繊維は,精製された酵母プリオン種子からインビトロで生成されました.
In vitroで生成された繊維は,酵母に導入されたときに株特有の感染性を示しました.
電子顕微鏡と difraktion は,種子と一致する繊維のクロスベータアミロイド構造を確認しました.
in vitroで生成された繊維の形態は,オリジナルの酵母種子と区別できなかった.

結論:

プリオン菌株は,たしかにタンパク質のみの実体である.
異なるプリオン株情報は,Sup35タンパク質の異なる自己増殖のクロスベータ折り畳みパターンにコード化されています.
この研究は,プリオン菌株の多様性と伝播の構造的基礎に対する強力な証拠を提供します.

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