内細胞AP2複合体の分子構造と機能モデル

Brett M Collins¹, Airlie J McCoy, Helen M Kent

¹Cambridge Institute for Medical Research, University of Cambridge, Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Hills Road, United Kingdom.

Cell

|June 28, 2002

まとめ

AP2コンプレックス AP2コンプレックス

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:

アダプタータンパク質2 (AP2) は,ヘテロテトラメリッククラスリンアダプター複合体で,膀の密輸に不可欠です.
AP2は,プラズマ膜の負荷を内部化するための重要なプロセスであるクラスリン媒介性エンドサイトーシスを媒介する.

研究の目的:

エンドサイトーシスにおけるAP2機能の構造的基礎を解明する.
AP2の脂質と内細胞モチーフとの相互作用を理解する.

主な方法:

X線結晶学を用いて,AP2核複合体の構造を決定した.
構造は2.6A解像度で解像しました.
この複合体は,ポリフォスファティディルニノシトールの模倣剤であるイノシトールヘキサキスファート (inositolhexakisphosphate) の存在下で研究されました.

主要な成果:

200 kDaのAP2コア複合体 (アルファ幹,β2幹,mu2,シグマ2) の構造が決定されました.
アルファおよびmu2サブユニットで,2つの潜在的なポリフォスファティディルノシチド結合部位が特定されました.
Yxxphi内細胞モチーフの結合部位は埋まっているので,結合には形状の変化が必要であることを示唆しています.

結論:

エンドサイトーシス中のAP2の募集と活性化のモデルが提案されています.
mu2リンカーの酸化は,Yxxphiモチーフ結合に必要な構造変化を誘発する可能性があります.
構造的な洞察は,クラスリン媒介性内分泌細胞の調節に関する理解を深める.

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