人間のトリアキルグリセロール合成酵素の構造と触媒機構
Xuewu Sui1,2, Kun Wang1,2, Nina L Gluchowski1,2,3
1Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Nature
|May 21, 2020
まとめ
研究者はヒトのDGAT1の構造を決定し,トリアシルグリセロール合成に不可欠な酵素である. この突破は 酵素を明らかにした
科学分野:
- 生物化学
- 構造生物学
- 分子生物学
背景:
- トライアキルグリセロールは産業用途の重要なエネルギー貯蔵物です.
- 過剰なトリアシルグリセロルの蓄積は肥満や代謝疾患に寄与する.
- アシル-CoAダイアシルグリセロールアシルトランスフェラーゼ (DGAT) 酵素はトライアシルグリセロール合成を触媒するが,その構造とメカニズムは不明である.
研究 の 目的:
- ヒトのDGAT1の構造を決定する.トライアキルグリセロール合成の鍵となる酵素.
- DGAT1の触媒メカニズムを解明する.
- トライアキルグリセロール合成を理解するための構造的基礎を提供する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) を用いて,ヒトの2次元のDGAT1の構造を決定した.
- 構造は約3.0 Åと3.2 Åの解像度で解像しました.
- ミュタゲネシスと機能研究が行われました.
主要な成果:
- ヒトDGAT1の二重構造が決定され,膜領域に活性サイトを持つホモディマーが明らかになった.
- オレオイル-コア基質の構造は,コアがシトソル側と,水害性チャネル内のアシル群に結合することを示した.
- リピドのような密度,潜在的にアシル受容体,反応センターで観察されました.
結論:
- DGAT1構造はトライアキルグリセロール合成のメカニズムに洞察を与えます.
- 構造的および機能的データに基づいたDGAT触媒によるトリアシルグリセロール合成モデルが提案されています.
- この研究は,DGAT酵素と代謝疾患に関するさらなる研究のための基礎を築きます.
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