Gタンパク質に結合したシグナリングシステムにおけるダイナミック・スキャフォल्डिंग

Prashant Mishra¹, Michael Socolich, Mark A Wall

¹Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.

Cell

|October 10, 2007

まとめ

ドロソフィラの光受容体におけるINADの支架は,リドックススイッチメカニズムを使用しています. PDZ5におけるこのダイナミックな形状の変化は,視覚信号と行動をミリ秒のスケールで制御する.

科学分野:

分子および細胞生物学
神経科学は神経科学である.
構造生物学構造生物学とは

背景:

INADスキャフォールドは,ドロソフィラの光受容体細胞の視覚信号伝導に不可欠であり,重要なマルチタンパク質複合体を組織します.
PDZドメインはタンパク質の相互作用モジュールとして知られていますが,その動的調節は依然として活発な調査の分野です.

研究の目的:

INADの構造ダイナミクスを調査し,特にPDZドメインのリドックス依存行動に焦点を当てました.
ビジュアルシグナル伝達と in vivo の行動に対する PDZ ドメインの構成変化の機能的影響を明らかにする.

主な方法:

異なる酸化還元状態のINAD PDZドメインの構造を決定するためのX線結晶学.
光に依存する二酸化硫化物結合形成を検出するための生体内生化学分析.
INAD変異タンパク質を発現するトランスジェニックドロソフィラの生成と行動分析.

主要な成果:

1つのINAD PDZドメイン (PDZ5) は,還元状態と酸化状態の間のリドックス依存型コンフォーメーションスイッチを経験します.
酸化状態は,分子内二硫化結合による歪んだリガンド結合部位を特徴としており,これはin vivoで光の曝露時に一時的に形成される.
減少状態に閉じ込められたPDZ5変異体を持つハエは,視覚応答の終了と視覚的に誘導された行動に深刻な欠陥を示します.

結論:

INADは,静的な支架ではなく,ダイナミックな分子マシンとして機能し,信号調節のためにコンフォメーションスイッチングを使用します.
PDZドメインのレドックス依存型構成の変化は,信号伝導のミリ秒時間スケールの調節のためのメカニズムを提供します.
この研究は,PDZドメイン調節の新しいメカニズムを明らかにし,信号伝達経路におけるダイナミックタンパク質複合体の機能を理解するための意味を持つ.

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