ストレス粒子のタンパク質の封じ込めは,細胞内での安定性に依存するが,In Vitroの折り畳み安定性には依存しない

Nirnay Samanta¹, Sara S Ribeiro¹, Mailin Becker¹

¹Institute of Physical and Theoretical Chemistry, TU Braunschweig, Rebenring 56, D-38106 Braunschweig, Germany.

Journal of the American Chemical Society

|November 17, 2021

まとめ

タンパク質の折りたたみ安定性ではなく, ストレス粒子の結合を決定する. この発見は熱ストレスで細胞がタンパク質の品質を制御する方法を明らかにしています

科学分野:

細胞生物学
バイオ物理学
タンパク質の生化学

背景:

ストレス粒子は,細胞ストレス中のタンパク質品質管理 (PQC) に不可欠な膜のない器官である.
SGに局限する特定のタンパク質の折り畳み状態とSG環境の役割は不明である.

研究の目的:

タンパク質の折り畳み安定性と結合傾向が,スーパーオキシドディスミュータゼ1 (SOD1) とSGの関連性をどのように影響するか調査する.
熱ストレスで細胞内のタンパク質分割を制御するメカニズムを解明する.

主な方法:

SOD1の局所性を調べる細胞研究
実験室での生体検査
コンピュータによるシミュレーション (in silico)

主要な成果:

細胞内のSGとのSOD1の関連性を決定するのは,タンパク質の折り畳み安定性である.
in vitroおよびin silicoデータは,展開されたタンパク質の柔軟性がGS関連におけるマイナーな要因であることを示しています.
特定のタンパク質とタンパク質の相互作用は,細胞質とSGの間に異なっており,折り畳み状態の分割に影響を与えます.

結論:

折り畳み安定性は,熱ストレス下でのSOD1のSGへの局所化の主要な決定因子です.
細胞のタンパク質とタンパク質の相互作用は,SGにタンパク質の相分離を調節する上で重要な役割を果たします.
タンパク質毒性ストレスに対する細胞の反応を理解するにはこれらの原理を理解することが重要です

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