9RSX

Structure of RACK1 bound to the C-terminus of SERBP1 and the RIH region of ZAK

これはPDB形式変換不可エントリーです。

9RSX の概要

• エントリーDOI: 10.2210/pdb9rsx/pdb
• EMDBエントリー: 54236
• 分子名称: Mitogen-activated protein kinase kinase kinase 20, Plasminogen activator inhibitor 1 RNA-binding protein, 40S ribosomal protein S3, ... (4 entities in total)
• 機能のキーワード: zak, collision, rsr, quality control, ribosome
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 198180.60

構造登録者

Niu, S.,Beckmann, R. (登録日: 2025-07-01, 公開日: 2025-12-10, 最終更新日: 2026-01-28)

主引用文献

Huso, V.L.,Niu, S.,Catipovic, M.A.,Saba, J.A.,Denk, T.,Park, E.,Cheng, J.,Berninghausen, O.,Becker, T.,Green, R.,Beckmann, R.
ZAK activation at the collided ribosome.
Nature, 649:1051-1060, 2026

PubMed Abstract: Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK. Despite the critical role of ZAK during cellular stress, a mechanistic and structural understanding of ZAK-ribosome interactions and how these lead to activation remain elusive. Here we combine biochemistry and cryo-electron microscopy to discover distinct ZAK-ribosome interactions required for constitutive recruitment and for activation. We find that upon induction of ribosome collisions, interactions between ZAK and the ribosomal protein RACK1 enable its activation by dimerization of its SAM domains at the collision interface. Furthermore, we discover how this process is negatively regulated by the ribosome-binding protein SERBP1 to prevent constitutive ZAK activation. Characterization of novel SAM variants as well as a known pathogenic variant of the SAM domain of ZAK supports a key role of the SAM domain in regulating kinase activity on and off the ribosome, with some mutants bypassing the ribosome requirement for ZAK activation. Collectively, our data provide a mechanistic blueprint of the kinase activity of ZAK at the collided ribosome interface.

PubMed: 41261136
DOI: 10.1038/s41586-025-09772-8

実験手法

ELECTRON MICROSCOPY (2.91 Å)