フォスフォリファーゼC-ガンマ1のSH2ドメインの核磁気共振構造は,高親和性結合ペプチドで複合している

S M Pascal¹, A U Singer, G Gish

¹Biochemistry Research Division, Hospital for Sick Children, Toronto, Ontario, Canada.

Cell

|May 6, 1994

まとめ

フォスフォリファーゼC-ガンマ1 1の構造

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:

SH2ドメインは,信号伝導に不可欠です.
フォスフォリファーゼC-ガンマ1 (PLC-ガンマ1) は,細胞の信号伝達経路に役割を果たしています.
SH2ドメインの相互作用を理解することは,信号伝達機構の解読の鍵です.

研究の目的:

PLC-ガンマ1のC端 SH2ドメインの溶液構造を決定する.
血小板由来成長因子受容体 (PDGFR) の特定のフォスフォペプチドによるその複合体を調査する.
SH2-フォスフォペプチド相互作用の構造的基礎を解明する.

主な方法:

核磁共振 (NMR) スペクトロスコピーを用いた.
この研究は,PLC-gamma 1 SH2ドメインとTyr-1021を含むフォスフォペプチドの複合体に焦点を当てた.

主要な成果:

PLC-ガンマ1 SH2-フォスフォペプチド複合体の全体的なトポロジーは,SrcおよびLck SH2複合体のトポロジーに似ています.
重要な違いは,C端末の残留物の結合部位がフォスフォチロジン (pTyr) に結合している点であった.
この部位は,ペプチド残基 +1 から +6 を pTyr に相対的に収納する延長された溝を形成します.

結論:

PLC-gamma 1 SH2ドメインは,SrcおよびLck.と比較して明確な結合モードを示しています.
この相互作用には,pTyr.へのC端末から水害性残留物が含まれています.
PLC-gamma 1 SH2ドメインは,SH2-フォスホペプチド相互作用の第2クラスのプロトタイプとして機能します.

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