ナトリウムポンプピロホスファタゼの構造と触媒サイクル

Juho Kellosalo¹, Tommi Kajander, Konstantin Kogan

¹Structural Biology and Biophysics Program, Institute of Biotechnology, Post Office Box 65, University of Helsinki, FIN-00014, Finland.

Science (New York, N.Y.)

|July 28, 2012

まとめ

膜統合型パイロフォスファタゼ (M-PPases) は,膜を横断してイオンをポンプする. この研究は,それらのイオンポンプメカニズムと,遺伝子の三重化による進化的起源を明らかにしています.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
分子生物学は分子生物学である.

背景:

膜統合型パイロフォスファタゼ (M-PPases) は,様々な生物において不可欠な酵素であり,イオン輸送を促進する.
これらの酵素は,ピロホスファートの水解/合成をナトリウム (Na+) または水素 (H+) イオンの動きとカップリングします.

研究の目的:

M-PP相におけるイオンポンプの構造的基礎を解明する.
基板結合とゲート開封のメカニズムを理解する.
M-PPasesの進化的起源を調査するために.

主な方法:

X線結晶学を用いて,Thermotogaの海洋M-PPaseの構造を2.6と4.0アングストームの解像度で決定した.
静止状態と製品複合体の状態の比較構造分析.

主要な成果:

静止状態の構造は,6つのアルファヘリクスのユニークな"結合ファネル"を明らかにし,水解センターを膜ゲートに接続します.
サブストラット結合は,ヘリックス12が下に滑り込み,結合変化メカニズムを通じてゲートを開き,形状の変化を誘導します.
構造的重置は,M-PPasesが遺伝子の三重化によって進化したことを示唆し,繰り返す螺旋状の配列によって示されています.

結論:

この研究は,M-PPasesのイオンポンプメカニズムに関する前例のない洞察を提供します.
ゲート制御のために,ヘリックス12を含む新しい結合変化メカニズムが提案されています.
証拠は,遺伝子三重化によるM-PPase起源の進化モデルを支持しています.

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