APC/Cの原子構造とタンパク質のユビキチン化メカニズム

Leifu Chang¹, Ziguo Zhang¹, Jing Yang¹

¹MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.

Nature

|June 18, 2015

まとめ

アナフェーズ促進複合体 (APC/C) 構造の研究は,Emi1がE2酵素を抑制し,Cdh1の相互作用を定義する方法を明らかにしています. これは,細胞分裂におけるAPC/C調節を理解するための枠組みを提供します.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
構造生物学構造生物学とは

背景:

アナフェーズ促進複合体 (APC/C) は,細胞サイクル移行を調節する重要なE3ユビキチンリガゼである.
APC/Cの活動は,共活性化剤,リン酸化,チェックポイントタンパク質によって厳密に制御されます.

研究の目的:

APC/C-コアクティベーター複合体の原子構造を決定する.
エミ1によるAPC/C阻害とCdh1による調節のメカニズムを解明する.
APC/C媒介ユビキチネーション反応についての洞察を得るために.

主な方法:

低温電子顕微鏡 (cryo-EM) を用いて,高解像度構造を得ました.
Emi1およびUbcH10-ubiquitin結合体を含むAPC/C複合体の構造分析.

主要な成果:

APC/C-Emi1およびAPC/C-UbcH10-ubiquitin複合体の原子構造が決定されました.
構造は,APC/Cサブユニットと触媒モジュールのアーキテクチャを明らかにします.
UbcH10とUbe2SのEmi1媒介抑制のメカニズムが定義されました.
Cdh1の相互作用とCdh1のリン酸化の影響が解明されました.
APC/Cによるユビキチネーションの開始に関する洞察が得られた.

結論:

この研究は,APC/C規制の詳細な構造的な理解を提供します.
これらの発見は,APC/C機能の将来のin vivo研究のための定量的な枠組みを提供する.
この結果は,細胞サイクル制御と染色体分離に関する知識をさらに深める.

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