Hsp104は,自己複製するSup35プリオンコンフォーマーの形成と除去を触媒として作用する

James Shorter¹, Susan Lindquist

¹Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

Science (New York, N.Y.)

|May 25, 2004

まとめ

タンパク質Hsp104は,低濃度でSup35アミロイド形成を促進し,高濃度で繊維を分解することによって,酵母プリオン [PSI+]の遺伝を調節し,遺伝パターンを説明します.

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.
イースト遺伝学イースト遺伝学

背景:

タンパク質再構成因子Hsp104は,酵母プリオン[PSI+]の遺伝に不可欠である.
プリオン[PSI+]は,翻訳終結因子Sup35.5の自己永続性アミロイドコンフォマーによって形成される.
Hsp104の過剰レベルと不十分なレベルの両方が[PSI+]の除去につながります.

研究の目的:

イーストのプリオン [PSI+] 相続におけるHsp104の二重の役割を調査する.
Hsp104濃度がSup35線維化とプリオン伝播に影響するメカニズムを解明する.
Hsp104の活性に基づく[PSI+]の観察された遺伝パターンを説明する.

主な方法:

精製されたHsp104およびSup35.5を用いたインビトロ研究.
Sup35 オリゴメリック中間物質のHsp104触媒による形成の分析.
新規Sup35フィブリル化に対するHsp104の効果の調査.
Hsp104による成熟したSup35繊維の分解の評価.

主要な成果:

低濃度では,Hsp104は,Sup35繊維の核形成に不可欠な,アミロイド原性オリゴマーの形成を触媒化する.
高濃度のHsp104は,アミロイドのオリゴメリゼーションとフィブリル化を阻害する.
Hsp104は成熟した繊維を分解し,最初は複製のための表面を露出したが,最終的にはプリオン絶滅につながった.
濃度に依存するHsp104の活性には,明確な反応メカニズムが根底にある.

結論:

Hsp104の濃度に依存する活動は,酵母プリオン[PSI+]の複雑な遺伝パターンを説明する.
アミロイド形成を促進し,抑制するHsp104の二重の役割は,プリオン安定性の鍵です.
Hsp104のメカニズムの理解は,タンパク質のみの遺伝とコンフォメーションテンプレートに関する洞察を提供します.

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