v-srcのフォスフォチロシン認識ドメインSH2の結晶構造は,チロシン酸化ペプチドで複合している

G Waksman¹, D Kominos, S C Robertson

¹Rockefeller University, New York.

Nature

|August 20, 1992

まとめ

v-src 腫瘍遺伝子は

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
腫瘍学腫瘍学

背景:

v-src腫瘍遺伝子の産物は,がんに関与するチロシンキナーゼである.
SH2ドメインは,チロシンリン酸化を含むタンパク質とタンパク質の相互作用を媒介するために重要である.
これらの相互作用を理解することは,標的治療の開発の鍵です.

研究の目的:

v-src腫瘍遺伝子の産物であるSH2ドメインの3次元構造を解明する.
SH2ドメインとフォスフォチロシルペプチドの間の結合相互作用を特徴付ける.

主な方法:

構造を特定するために,X線結晶学を用いた.
2つの複合体に対して高解像度 (1.5と2.0A) のデータを収集した.

主要な成果:

SH2ドメイン構造は,アルファヘリックスに囲まれた中央の反並列ベータシートを特徴としています.
ペプチド結合はベータシート,ループ,アルファヘリックスで起こります.
特定のフォスフォチロシンの認識には,水素結合とアミノアロマティック相互作用 (ライシン,アルギニン) が含まれる.

結論:

決定された構造は,SH2ドメイン-フォスフォチロシルペプチドの認識に関する詳細な洞察を提供します.
この構造情報は,v-srcシグナル伝達経路を標的にする阻害剤の設計に役立つ.

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