アラビドプシス・タリアナの2孔チャンネルTPC1の構造,抑制および調節

Alexander F Kintzer¹, Robert M Stroud¹

¹Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.

Nature

|March 11, 2016

まとめ

植物の二孔チャネル (TPC) の結晶構造は,それらのイオン流を制御し,どのように調節されているかを明らかにします. これはエボラウイルス感染症の機能や潜在的薬剤標的の洞察を与えてくれます

科学分野:

構造生物学
分子生理学
植物学

背景:

二孔チャネル (TPC) は,エヌカリオットイオンチャネルで,イオンフルス,pH,およびエンドリソソーム区間のトラフィックを調節する.
TPCは細胞のプロセスに不可欠であり,エボラウイルスを含むウイルス感染症に関与しています.

研究の目的:

アラビドプシス・タリアナ TPC1の結晶構造を決定する.
イオン浸透,チャネル活性化,電圧による調節,イオン,リン酸化のメカニズムを解明する.

主な方法:

2.87 Å の解像度のX線結晶学
構造分析により,電圧感知領域と規制領域を特定する.

主要な成果:

TPC1の結晶構造は,イオン浸透と活性化のための重要な特徴を明らかにします.
カルシウム活性化をアロステリックに調節する酸化部位が特定されました.
異なる形状を示す電圧感知領域 (VSD2) が特徴付けられました.
ファルマコフォアトランス-Ned-19はVSD2にアロステリックに結合し,毛穴ドメインをクランプすることが示された.

結論:

TPC1構造は,TPCチャネル機能と規制を理解するための基礎を提供します.
構造的な洞察は,ウイルス感染症や他の疾患に対するTPCを標的とした治療法の開発を導くことができます.

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