ユカリオットオリゴサカリトランスフェラーゼ複合体の原子構造

Lin Bai¹, Tong Wang², Gongpu Zhao³

¹Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, USA.

Nature

|February 22, 2018

まとめ

研究者らは,タンパク質のN-グリコシル化に不可欠なオリゴサカリルトランスフェラーゼ (OST) 複合体の構造を明らかにした. この発見は共翻訳的改変過程を明らかにし,標的の阻害剤の開発に役立ちます.

科学分野:

構造生物学
分子生物学
生物化学

背景:

N-グリコシレーションは,約90%の真核糖タンパク質に影響を与える重要な翻訳後の変化です.
エンドプラズマ網膜にあるオリゴサカリルトランスフェラーゼ (OST) 複合体は,この重要なプロセスを触媒化する.
限られた高解像度構造データは,真核タンパク質のN-グリコシル化メカニズムを深く理解することを妨げています.

研究の目的:

Saccharomyces cerevisiae OST複合体の高解像度構造を決定する.
共同翻訳タンパク質のN-グリコシレーションの構造的基礎を解明する.
N-グリコシレーションを標的とする小分子阻害剤の潜在的な開発に関する洞察を提供するためです.

主な方法:

クリオ電子顕微鏡 (cryo-EM) を用いて,OST複合体の3. 5 Å解像度構造を達成した.
決定された構造には,Ost1-Ost5,Stt3,Wbp1,Swp1を含む主要なサブユニットが含まれています.

主要な成果:

凍結-EM構造は OST複合体とその構成部分の詳細な構造を明らかにした.
7つのフォスフォリピドが複合体内のサブユニット間の相互作用の媒介者として特定されました.
Stt3 N- グリカンは,ER ルーメンにおけるWbp1およびSwp1との相互作用を媒介することが観察された.
サブユニットOst3はSec61トランスロコンとインタフェースし,新生ペプチドを触媒部位に誘導する.

結論:

高解像度構造は,同翻訳タンパク質のN-グリコシレーションのメカニズムに前例のない洞察を提供します.
OST複合体の構造とその相互作用を理解することで,グリコシレーション経路を標的とした新しい治療戦略の道を開くことができます.

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