SIRT6は,長鎖脂肪酸アシルリジンの水解によってTNF-αの分泌を調節する

Hong Jiang¹, Saba Khan, Yi Wang

¹Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.

Nature

|April 5, 2013

まとめ

人間のSIRT6酵素は,脂肪アシル基をタンパク質から除去し,タンパク質分泌を調節する新しいメカニズムを明らかにし,翻訳後の修正に関する洞察を提供します.

科学分野:

バイオケミストリーバイオケミストリー
分子生物学は分子生物学である.
細胞生物学細胞生物学

背景:

サートゥイン (Sir2ファミリー) は,転写,ゲノム安定性,代謝,寿命に関与するNAD依存型脱酸化酵素である.
哺乳類のサートゥイン7種のうち4種は, in vitro 脱セチラゼ活性が弱く,代替的な機能を示唆しています.
タンパク質リジン脂肪アシレーションは,解明されていない機能と調節を持つ既知の哺乳類の改変である.

研究の目的:

人間のSIRT6の酵素活性を脱エチル化を超えて調査する.
タンパク質の翻訳後の改変におけるSIRT6の役割を明らかにする.
タンパク質ライシン脂肪アシレーションの機能的影響を理解するために.

主な方法:

酵素活性測定は,SIRT6が脂肪酸アシル基を除去する能力を評価する.
SIRT6の基板特異性の構造的基礎を決定するためのX線結晶学.
腫瘍死滅因子アルファ (TNF-α) の分泌にSIRT6の影響を実証する生化学実験.

主要な成果:

人間のSIRT6は,ライシン残基から長鎖脂肪アシル基を効率的に除去します.
SIRT6の結晶構造は,脂肪酸アシル鎖を収納する水性ポケットを明らかにしています.
SIRT6は,K19およびK20残基の脂肪アシレーションを除去することによって,TNF-αの分泌を促進します.
タンパク質リジン脂肪アシレーションは,タンパク質分泌の新たな規制メカニズムとして特定されています.

結論:

SIRT6は,既知の脱セチラゼ機能とは異なる,有意な脂肪アシラゼ活性を持っています.
タンパク質リジン脂肪アシレーションは,タンパク質分泌を調節する新発見のメカニズムです.
SIRT6の脂肪アシレーションにおける役割は,あまり研究されていないこの翻訳後の改変を研究するための新しい道を開きます.

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