大規模な形状の変化は,AP2クラスリンアダプター複合体内の貨物結合に膜の採用を結びつける
Lauren P Jackson1, Bernard T Kelly, Airlie J McCoy
1Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Cell
|July 7, 2010
まとめ
AP2アダプター・コンプレックスは構造変化を起こし,貨物結合部位のブロックを解除する. この構造的なシフトは,AP2を容易にする.
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.
- バイオケミストリー バイオケミストリー
背景:
- AP2アダプター複合体は,クラスリン媒介の内分細胞形成に不可欠である.
- AP2は,PtdIns4,5P(2) を含んだ膜を介して,トランスメブランの貨物をクラトリンの支架と結びつける.
- 細胞溶液の形態では,AP2の貨物結合部位はβ2サブユニットによって遮断されます.
研究 の 目的:
- AP2活性化の構造的メカニズムを解明する.
- AP2が"ロック"状態から"オープン"状態へのトランジションをどのように理解するか.
- PtdIns4,5P(2) がAP2媒介性エンドサイトーシスにおける役割を調査する.
主な方法:
- タンパク質結晶学を用いてAP2の構造を決定した.
- AP2-膜の相互作用を研究するために,生体物理学的技術が採用されました.
- AP2サブユニットの構成の変化を分析した.
主要な成果:
- AP2は,mu2 (C-mu2) のC端末ドメインの移転により,重要な形状変化を経験します.
- この再配置は,YxxPhiと[ED]xxxL[LI]の両方の内細胞モチーフ結合部位をブロック解除します.
- 4つのPtdIns4,5P(2) 結合部位と2つの貨物結合部位はコプラナーになります.
- AP2がPtdIns4,5P(2) を含んだ膜と相互作用すると,内皮細胞の負荷結合が起こります.
結論:
- AP2の形状の柔軟性は,エンドサイトーシスにおけるその機能に不可欠である.
- PtdIns4,5P(2) と貨物モチーフへの同時結合は,結合部位のコプラナー配置によって容易にされる.
- PtdIns4,5P(2) との膜相互作用は,AP2の内細胞の荷重徴集の主な原動力である.
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