フォトアフィニティベースのプロテオミクスを用いたポリ (ADP-リボス) 結合タンパク質の識別
Morgan Dasovich1,2, Morgan Q Beckett3, Scott Bailey2,3
1Department of Chemistry, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Journal of the American Chemical Society
|February 17, 2021
まとめ
研究者らは,DNA 損傷反応における重要な分子である ポリアドプリボース (PAR) に結合するタンパク質を特定しました. この研究では,RNAの処理と代謝に関与する新しい PAR結合タンパク質が発見され,がん治療の理解が進んでいます.
科学分野:
- 生物化学
- 分子生物学
- プロテオミクス
背景:
- ポリアドプリボゼ (PAR) はDNA損傷反応に不可欠であり,がん治療の標的である.
- PARの分子機能と結合パートナーは,まだ完全に理解されていません.
- PAR結合タンパク質を特定することは,PARシグナル伝達経路を明らかにするために不可欠です.
研究 の 目的:
- 固有のポリー ((ADP-リボース) (PAR) 結合タンパク質を特定するための方法を開発する.
- 新しい候補を含む PAR 結合タンパク質の包括的な検定を作成する.
- タンパク質結合とシグナル伝達における PARポリマー長さの役割を調査する.
主な方法:
- 新しい PAR フォトアフィニティ・プローブの合成
- 内生性PAR結合タンパク質の親和性捕獲と分離
- プルダウンと電離運動移転測定を用いてPAR結合の確認
- 定義された長さの PARプローブを使用してタンパク質結合選択性の分析.
主要な成果:
- 数十の既知のタンパク質と 数百の新しいPAR結合タンパク質の特定
- 8つの新しい候補タンパク質に対する PAR結合の確認
- 長さ依存の PAR 結合の実証,タンパク質はより長い PAR 鎖 (40-mer 対 8-mer) を好む.
- PAR結合とRNA代謝と生物分子凝縮物形成の関連
結論:
- この研究は,PAR結合タンパク質の最初の包括的な検定を提供します.
- PARポリマーの長さは,PARタンパク質の相互作用とシグナル伝達の重要なレギュラーである.
- 新しく発見された PAR結合タンパク質は,がんやその他の疾患の治療対象となる可能性がある.
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