HCF-1は,O-GlcNAcトランスファーゼの活性部位に裂かれます
Michael B Lazarus1, Jiaoyang Jiang, Vaibhav Kapuria
1Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|December 7, 2013
まとめ
O-リンクされたN-アセチルグルコサミン (O-GlcNAc) トランスファーゼ (OGT) は,宿主細胞因子-1 (HCF-1) をその活性部位内で割ります. これは,O-GlcNAcタンパク質のグリコシル化とHCF-1分裂が同じ酵素部位を共有していることを示しています.
科学分野:
- 分子および細胞生物学
- バイオケミストリー バイオケミストリー
- 翻訳後の修正 翻訳後の修正
背景:
- ホスト細胞因子-1 (HCF-1) は,ヒトの細胞サイクル進行を調節する上で極めて重要です.
- HCF-1は,繰り返された配列の割れ目を伴うタンパク質分解の成熟を経験します.
- O-リンクされたN-アセチルグルコサミン (O-GlcNAc) トランスファーゼ (OGT) は,このプロセスに関与する栄養素反応性酵素です.
研究 の 目的:
- OGTがHCF-1を割る分子メカニズムを解明する.
- OGTとHCF-1の相互作用の構造的基盤を調査する.
- HCF-1の分裂とO-GlcNAcのグリコシル化が同じ活性部位で起こるかどうかを判断する.
主な方法:
- HCF-1とのOGTテトラトリコペプチド-リピートドメイン相互作用の構造分析.
- OGTによるHCF-1リピートの割れ方を研究するための生化学的分析.
- HCF-1の分裂部位を変更するためのサイト指向型変異.
主要な成果:
- OGTのテトラトリコペプチドリピートドメインは,HCF-1リピートのカルボキシル端末と結合する.
- HCF-1分裂部位は,OGT活性部位内に位置し,尿素二酸化塩酸-GlcNAc結合ポケットの近くにあります.
- システインとグルタミン酸残留物の間で割れが起こり,ピログルタミン酸製品を形成します.
- 分裂部位のグルタミン酸をセリンに変異させると,HCF-1がグリコシライゼーション基板を繰り返します.
結論:
- HCF-1のタンパク質分裂とO-GlcNAcのタンパク質グリコシレーションは,同じ活性部位内のOGTによって触媒化されます.
- この発見は,HCF-1の成熟とO-GlcNAcの改変の間のメカニズム的リンクを提供する.
- この研究は,タンパク質加工におけるOGT活性部位の二重な機能を明らかにした.
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