Shccのフォスフォチロジン結合ドメインの構造とリガンド認識

M M Zhou¹, K S Ravichandran, E F Olejniczak

¹Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.

Nature

|December 7, 1995

まとめ

Shcタンパク質は,Shcというタンパク質です.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
分子生物学は分子生物学である.

背景:

ティロシン・リン酸化タンパク質は,細胞シグナル伝達において重要な役割を果たします.
タンパク質とタンパク質の相互作用を理解することは,信号伝達経路の解読の鍵です.
Shcタンパク質のフォスフォチロジン結合ドメイン (PTB) は,信号伝導に関与しています.

研究の目的:

Shc PTB ドメインによるフォスフォチロジン結合の構造的基礎を解明する.
PTBドメインのフォスフォペプチド認識機構を,SH2ドメインのような他の既知のドメインと比較する.
PTBドメイン構造の潜在的な機能的影響を調査する.

主な方法:

核磁共振 (NMR) スペクトロスコピーは,構造を決定するために使用されました.
この研究では,Shc PTBドメインをフォスフォペプチドで複合させた.

主要な成果:

フォスホペプチドは,タンパク質ベータシートと対パラレルベータ鎖を形成することによって,PTBドメインと結合します.
重要なフォスフォチロジン残留物 (pY-5) は,PTB領域内の水嫌性ポケットと相互作用する.
フォスフォペプチドは結合時にβ-ターン形状を採用する.
PTBドメインは,プレックストリンホモロジー (PH) ドメインと構造的に類似しています.

結論:

Shc PTB ドメインは,SH2 ドメインと比較して,チロシン・リン酸化タンパク質を認識するための独特なメカニズムを使用しています.
PHドメインとの構造的類似性と,フォスフォリピドとの観察された結合は,膜局所化における役割を示唆している.
この発見は,細胞シグナル伝達におけるフォスフォタンパク質認識の代替方法についての洞察を提供します.

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