プロリンにおけるシス・トランス・イソメリゼーションは,神経伝達物質によるイオンチャネルの孔を開く

Sarah C R Lummis¹, Darren L Beene, Lori W Lee

¹Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.

Nature

|November 11, 2005

まとめ

5ヒドロキシトリプタミン3型 (5-HT3) 受容体

科学分野:

神経科学は神経科学である.
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:

5ヒドロキシトリプタミン3型 (5-HT3) 受容体はCysループ受容体である.
神経伝達物質の結合は,未知の形状の変化によってイオンチャネルゲーティングを誘導する.

研究の目的:

5-HT3受容体における神経伝達物質結合とチャネルゲーティングを結びつけるメカニズムを解明する.
M2-M3ループにおける特定のプロリン残留物 (Pro 8*) の役割を調査する.

主な方法:

不自然なアミノ酸変異により,プロリン類の8*位置にプロリン類を組み込む.
ミュータントチャネルの機能的特徴.
M2-M3ループペプチドに関する核磁気共振 (NMR) 研究.

主要な成果:

トランスフォーマーを好むプロリン類は,非機能的なチャネルをもたらしました.
プロリンアナログのシストランスエネルギーとチャネル活性化との間には相関関係がある.
NMR研究では,M2-M3ループペプチドの2つの異なる構造形態が明らかになりました.

結論:

Pro 8* のシストランスイソメリゼーションは,5-HT3受容体のゲーティングのための分子スイッチとして作用します.
このイソメリゼーションは,神経伝達物質の結合をチャネル開通と結びつける.
M2-M3ループ構造とPro 8*は受容体の機能に不可欠です.

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