リボソームによる血管新生活性化の構造的メカニズム

Anna B Loveland¹, Cha San Koh², Robin Ganesan³

¹RNA Therapeutics Institute, UMass Chan Medical School, Worcester, MA, USA. anna.loveland@umassmed.edu.

Nature

|May 8, 2024

まとめ

細胞系リボソームは血管新生酵素を活性化します血管新生酵素は癌などの病気に関わっている酵素ですリボソームはtRNAを血管新生素に誘導し,その触媒的活性と潜在的な治療薬の特異性を高めます.

科学分野:

生物化学
分子生物学
構造生物学

背景:

アンジオゲニンはRNase-Aタンパク質で血管新生,がん,神経変性疾患に関与しています
活性化された血管新生素はtRNAを分裂させ,翻訳抑制を引き起こすが,その活性化と特異性のメカニズムは不明であった.

研究の目的:

アンジオゲニンの活性化メカニズムとtRNA特異性を明らかにする.
血管新生素の触媒活性が制御される仕組みを理解する

主な方法:

生化学的測定法
低温電子顕微鏡 (cryo-EM) で,80Sリボソームに結合した血管新生素の構造を決定する.

主要な成果:

細胞リボソームは血管新生素の活性化剤として作用する.
Cryo-EM構造は,80SリボソームA部位に結合した血管新生素を示し,そのC端尾はRNase活性化のために再配置されています.
リボソームはtRNA基質をアンジオゲニンの活性部位に誘導し,特異性を与える.

結論:

リボソームは,その触媒中心を再配置し,tRNA分裂の特異性因子として作用することによって,血管新生素を活性化します.
血管新生素の活性化は,細胞のストレスで増加する空白のA位を持つリボソームと関連しています.
がんや神経変性疾患の治療薬の開発に役立つかもしれない.

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