Dictyostelium--a dipeptide model systemのSkp1におけるPro(143) の翻訳後の改変に関連した形状の変化は,二ペプチドモデルシステムであるディクチオステリウムのSkp1に含まれている
Chamini V Karunaratne1, Thomas K Weldeghiorghis, Christopher M West
1Department of Chemistry, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
Journal of the American Chemical Society
|September 25, 2014
まとめ
プロリル水酸化と糖酸化のような翻訳後の改変により,タンパク質の構成が変化します. SCFユビキチンリガゼのサブユニットであるSkp1のこれらの変化は,酸素感知とタンパク質相互作用に影響します.
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:
- SCFのユビキチンリガゼサブユニットSkp1はプロリル水酸化とグリコシル酸化を経験する.
- これらの変更は,Skp1の形状,F-ボックスタンパク質の相互作用,および有機体の酸素感知に影響を及ぼします.
- これらの変化の分子基盤を理解することは極めて重要です.
研究 の 目的:
- プロリル水酸化と糖酸化がSkp1の構成とペプチド結合のダイナミクスを影響する分子機構を調査する.
- タンパク質の構造と機能を調節する翻訳後の改変の役割を明らかにする.
主な方法:
- 末端を覆ったThr-Proダイペプチドの合成,様々な改変.
- (1) Hおよび (13) C NMRを含む核磁気共振 (NMR) スペクトロスコーピーは,形状と化学的シフトを分析するために使用されます.
- シス・トランス・イソメリゼーションの反応速度を決定するための磁気化移転実験.
- 空間的近接性を評価するための核オーバーハウザー効果 (NOE) 実験.
主要な成果:
- 変換変換に対する好みの増加は,次の順序で観察されました: Pro <ヒドロキシプロリン (Hyp) <グリコシル化ヒドロキシプロリン ([α-(1,4) GlcNAc]Hyp).
- プロリンの水酸化により,トランス-シス変換の速度が低下し,シス-トランス変換の速度が増加した.
- NOEの実験では,N端のThr残基のサイドチェーンが,砂糖分子がピロリジン環から離れる方向に影響することを示した.
結論:
- Skp1におけるプロリン残基の翻訳後の改変は,ペプチド結合の構成とイソメリゼーションのダイナミクスを著しく変化させる.
- これらの形状の変化は,Skp1の機能と全長タンパク質の酸素感知にどのように変化が影響するかの分子メカニズムを提供します.
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