Hsp90-Tau複合体は,シャパロン作用の特異性の分子基盤を明らかにしています

G Elif Karagöz¹, Afonso M S Duarte², Elias Akoury³

¹Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.

|March 4, 2014

まとめ

分子チャペロンであるヒートショックタンパク質70 (Hsp70) とヒートショックタンパク質90 (Hsp90) は,タンパク質の折り畳みを管理する. 新しいモデルは,Hsp90が後期折りたたみの中間物質と,Tau.のような本質的に乱れたタンパク質を認識する方法を示しています.

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:

細胞タンパク質の折り畳みは,主にHsp70とHsp90.0である分子チャペロンシステムによって制御されます.
Hsp70は早期に機能し,Hsp90はタンパク質の折りたたみ経路で後で作用する.
Hsp90の基板特異性と正確なタイミングメカニズムは,まだ十分に理解されていません.

研究の目的:

Hsp90の基板特異性の分子基礎を解明する.
Hsp90が遅い折りたたみの中間物質を早期のものと区別する方法を理解するために.
Hsp90とその疾患関連基質であるタウタンパク質の相互作用をモデル化するために.

主な方法:

Hsp90-Tau複合体の構造モデルの生成.
Hsp90基板結合インターフェースの分析.
ヒドロホビック残留物に対するHsp90の認識機構の調査.

主要な成果:

Hsp90は,集積傾向のある領域を含むタウタンパク質に広く結合します.
大きなHsp90結合インターフェイス (106 Å) は,多数の低親和接触を容易にします.
Hsp90は,Hsp70の結合部位とは異なる,遅い折りたたみの中間物質の散らばった水性残基を認識します.

結論:

Hsp90の幅広い,低親和の結合メカニズムは,遅い折りたたみの中間物質に対する特異性を説明します.
このメカニズムは,Hsp90が本質的に無秩序なタンパク質に結合する能力も説明しています.
構造モデルは,Hsp70とHsp90のチャペロンシステム間の機能的な調整の洞察を提供します.

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