Na+結合神経伝達物質のトランスポーターホモログの基板調節ゲートダイナミクス
Yongfang Zhao1, Daniel S Terry, Lei Shi
1Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.
Nature
|April 26, 2011
まとめ
神経伝達物質のシンポーターは,神経伝達物質を回収するためにNa ((+)) グラデーションを使用します. 細胞外部での基板結合は,細胞内ゲート開きを制御し,輸送効率を高め,隠されたNSS輸送機構を明らかにします.
科学分野:
- 神経科学は神経科学である.
- 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
背景:
- ニューロントランスミッター/Na(+) シンポーター (NSSs) は,Na(+) 共同輸送経由でニューロントランスミッターを再捕獲することによって,ニューロンの信号伝達を終了させます.
- ドーパミン,セロトニン,ノルアドレナリンの主要なNSSは,精神刺激薬と抗うつ薬の標的である.
- プロカリオットNSSの同類であるLeuTの結晶構造は,閉ざされた形状と外向きに開かれた形状を明らかにし,機能的メカニズムの研究を導いた.
研究 の 目的:
- Na(+) 結合輸送中に LeuT の構造的移行に基板結合がどのように結合されるかを調査する.
- 細胞内ゲートダイナミクスと輸送効率の制御における細胞外基質結合の役割を明らかにする.
主な方法:
- 輸送ダイナミクスを調べるために,ルシンよりも約10倍速く輸送される基板であるアラニンを利用しました.
- 先進的なイメージング技術を使用して,LeuTの細胞内ゲート領域でアラニン誘発のダイナミクスを観察しました.
- 主要な (S1) と二次的な (S2) 細胞外結合部位間の基板結合協力性を調査した.
主要な成果:
- 細胞外側での基質結合は,細胞内ゲートの開きと基質の解放を促進します.
- 細胞内ゲートのアラニン誘発のダイナミクスは,輸送効率と直接相関しています.
- S1とS2の部位で協力的な基板結合を特定し,30年以上の細胞内ゲート制御を行いました.
結論:
- NSS輸送メカニズムの機能的に重要な,以前は隠されていた側面を明らかにしました.
- 細胞外前庭における第2基板 (S2) 結合部位の重要な役割を強調した.
- 協同結合が示され,細胞内ゲートを制御し,Na(+) のグラデント駆動輸送を可能にします.
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