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人間の腸内微生物群の支配的なメンバーによる栄養素獲得の構造的基礎

Amy J Glenwright¹, Karunakar R Pothula², Satya P Bhamidimarri³

¹Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

|January 13, 2017

まとめ

腸内微生物の細菌外膜トランスポーター (SusCD) は,栄養素を輸入するために新しい"ペダルビン"メカニズムを使用します. この発見はヒトと微生物の共生と栄養素の吸収について重要な洞察を与えてくれます

科学分野:

微生物学
構造生物学
生物化学

背景:

大腸の微生物群は人間の健康と栄養に重要な役割を果たします
バクテリオデテス属は,粉利用システム (sus) のようなポリサッカリド利用ロキーを用いて食事中のグリカンを分解する.
外膜インポートはSusCのようなトランスポーターとSusDのようなリポタンパク質に依存し,ほとんど未知の機能を持つSusCD複合体を形成します.

研究の目的:

Bacteroides thetaiotaomicron の SusCD 複合体によって外膜に栄養素が転移するメカニズムを解明する.
これらの重要なバクテリアトランスポーターによって媒介された基板の輸入の構造的基礎を決定する.

主な方法:

2つの異なるSusCD複合体の高解像度構造を得るためのX線結晶学.
タンパク質の動態と基板の転移を分析する分子動態シミュレーション
シングルチャネル電気生理学でトランスポーター活動を研究する

主要な成果:

SusCトランスポーターはホモダイマーを形成し,各プロトメアは SusDによってカバーされ,インターフェースでリガンド結合腔を形成する.
細胞外基板の結合部位を露出させるため,SusDがヒンジのような動きを経験する"ペダルビン"メカニズムが明らかになった.
リガンド結合は,SusC-SusDインターフェースの大きな溶媒を除外された腔内で行われます.

結論:

この研究は,細菌の外膜SusCD複合体による栄養素の輸入のための新しい"ペダルビン"メカニズムを明らかにしています.
これらの発見は人と微生物の共生を理解するために不可欠な腸内細菌の栄養素の獲得方法に関する機械的洞察を提供します
構造的およびダイナミックなデータは,基板特異性およびトランスポーター規制に関する将来の研究のための基礎を提供します.

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