クリプトクローム・タイムレス構造は,昼夜時計のタイミングメカニズムを明らかにする

Changfan Lin¹, Shi Feng¹, Cristina C DeOliveira¹

¹Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.

Nature

|April 26, 2023

まとめ

フライの昼夜時計

科学分野:

シルカディアンリズムの分子機構
生体時計タンパク質の構造生物学
昆虫の生理学と適応

背景:

シルカディアンリズムは遺伝子発現の振動を通して行動や病気を制御します
ハエではTimeless (タイムレス) がPeriod (パー) の核入りを媒介し,Cry (クリプトクローム) はTimの光分解を誘発する.
昼夜時計内の分子相互作用を理解することはその調節的役割を解読するのに極めて重要です

研究の目的:

クリプトクローム (Cry) の標的であるタイムレス (Tim) の認識の構造的基礎を解明する.
ライトセンシングの暗号クロームがタイムレスとどのように相互作用し昼夜時計の機能に影響するかを調べるため
タイムレスポリモルフィズムと異なる気候への適応の構造的メカニズムを探求する.

主な方法:

クリプトクローム・タイムレス複合体の冷凍電子顕微鏡 (cryo-EM)
タンパク質とタンパク質の相互作用とコファクター結合の構造分析
核の輸入規制におけるタンパク質のリン酸化の役割を調査する.

主要な成果:

クライはタイムレス・アーマディロ・リピートとティム・ヘリクスの連続した核に結合します
Cryのフラビンコファクターは構造変化を起こし,分子界面で大規模な再配置を引き起こします.
リン酸化したTimセグメントはImportin-α結合を調節し,Tim-Per核インポートに影響を与える.
ティムのN端は再構築されたCryポケットに挿入され,光が放出されたC端の尾を入れ替えます.

結論:

この研究は光感受性Cryptochromeがタイムレスと認識し相互作用する分子機構を明らかにした
構造的な洞察はクリプトクローム媒介のタイムレス崩壊がハエの昼夜時計を調節する方法を説明します
この発見はタイムレスポリモルフィズムに構造的基盤を提供し異なる気候への適応を説明しています

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