構造生物学 構造生物学について デルタ型4のNotch1の関与の構造的基礎
Vincent C Luca1, Kevin M Jude1, Nathan W Pierce2
1Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|February 21, 2015
まとめ
ノッチ受容体は,ジャッジドおよびデルタ型 (DLL) タンパク質を通じて細胞運命を制御する. Notch1のO-リンクされたグリコシライゼーションはDLL4の結合に不可欠であり,細胞シグナル伝達における糖類の化学的役割を明らかにしている.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 構造生物学 構造生物学とは
背景:
- ノッチ受容体は,哺乳類の細胞運命を決定する上で極めて重要です.
- ジャッジドおよびデルタ型 (DLL) タンパク質は,ノッチ受容体の重要なリガンドである.
- O-リンクされたグリコシライゼーションは,ノッチタンパク質で発見された翻訳後の改変である.
研究 の 目的:
- Notch1-DLL4相互作用の構造的基礎を解明する.
- リンガンド結合におけるNotch1 O-リンクドグリコシレーションの役割を調査する.
- 翻訳後の改変がノッチシグナル伝達にどのように影響するかを理解する.
主な方法:
- 2.3アングストームの解像度でNotch1-DLL4複合体の構造を決定するためのX線結晶学.
- Notch1とDLL4.4のタンパク質相互作用の分析
- グライコシル化Notch1ドメインの生化学的および構造的特徴.
主要な成果:
- 結晶構造は,Notch1とDLL4の間の2箇所,反並列の結合方向性を明らかにした.
- Notch1の表皮成長因子のような繰り返し11と12は,DLL4のDSLとMNNLドメインと相互作用する.
- Notch1上のO-フコゼとO-グルコースは,代替アミノ酸として作用し,DLL4との重要な接触を形成します.
結論:
- O-リンクされたグリカンは,Notch1-DLL4の結合に直接的な化学的役割を果たします.
- ノッチのシグナル伝達能力は,発達的に調節されたグリコシライゼーション経路と関連しています.
- この研究は,ノッチ-リガンド相互作用の構造的および化学的基礎を提供します.
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