オメガ3脂肪酸の血脳障壁を通過する構造的基礎

Rosemary J Cater¹, Geok Lin Chua², Satchal K Erramilli³

¹Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.

Nature

|June 17, 2021

まとめ

脳へのドコサヘキサエノ酸の輸送は,神経学的健康に不可欠なトランスポーターであるMFSD2Aに依存しています. この研究はMFSD2Aを明らかにしています.

科学分野:

神経科学
構造生物学
生物化学

背景:

ドコサヘキサエノ酸 (DHA) は脳と目の発達に不可欠です.
食中のDHAは,MFSD2Aによってリソファティディルコリン経由で脳に輸送されます.
MFSD2Aは,DHAの吸収に重要なファシリテータースーパーファミリートランスポーターです.

研究の目的:

MFSD2Aの構造を決定する
障壁を越えた Na+依存型リソリピド輸送のメカニズムを解明する.
神経治療薬の投与に関する洞察を提供するためです

主な方法:

単粒子冷凍電子顕微鏡
ネイティブ・マススペクトロメトリー
機能分析
分子ダイナミクスシミュレーション

主要な成果:

MFSD2Aの構造は,内向きの形状で12のトランスメブランヘリクスを明らかにします.
大量のアンフィパシー腔には,Na+結合部位と結合されたリソリピド基板が含まれています.
Na+に依存する形状の変化は,横のゲート経由で基板の放出を促進します.

結論:

この構造は,MFSD2Aの異常な輸送メカニズムについての分子洞察を提供します.
MFSD2Aの機能を理解することは,脳の脂質吸収を理解するのに役立ちます.
この研究は,神経療法薬の投与戦略に役立つかもしれません.

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