EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	ZAK activation at the collided ribosome.
ジャーナル・号・ページ	Nature, Vol. 649, Issue 8098, Page 1051-1060, Year 2026
掲載日	2025年11月19日
著者	Vienna L Huso / Shuangshuang Niu / Marco A Catipovic / James A Saba / Timo Denk / Eugene Park / Jingdong Cheng / Otto Berninghausen / Thomas Becker / Rachel Green / Roland Beckmann /
PubMed 要旨	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. ...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.
リンク	Nature / PubMed:41261136 / PubMed Central
手法	EM (単粒子)
解像度	2.2 - 3.0 Å
構造データ	EMDB-54140: Cryo-EM map of the stalled 80S from the ZAK-bound human disome 手法: EM (単粒子) / 解像度: 2.35 Å EMDB-54141: Cryo-EM map of the collided 80S from the ZAK-bound human disome 手法: EM (単粒子) / 解像度: 2.35 Å EMDB-54147: Local refined map focusing on ZAK-RACK1 of the collided 80S 手法: EM (単粒子) / 解像度: 2.5 Å EMDB-54148: Local refined cryo-EM map focusing on ZAK-RACK1 of the stalled 80S 手法: EM (単粒子) / 解像度: 3.0 Å EMDB-54149: Cryo-EM map of the hybrid state translating 80S 手法: EM (単粒子) / 解像度: 2.2 Å EMDB-54150: Cryo-EM map of the hibernating 80S 手法: EM (単粒子) / 解像度: 2.6 Å EMDB-54165: Cryo-EM map of reconstituted ZAK-RBR-40S 手法: EM (単粒子) / 解像度: 2.3 Å EMDB-54166: Cryo-EM map of the stalled 80S from ZAK-K394D-disome 手法: EM (単粒子) / 解像度: 2.95 Å EMDB-54167: Cryo-EM map of the collided 80S from ZAK-K394D-disome 手法: EM (単粒子) / 解像度: 2.95 Å 54172 9rpv EMDB-54172, PDB-9rpv: Structure of the ZAK-bound human disome 手法: EM (単粒子) / 解像度: 2.35 Å 54236 9rsx EMDB-54236, PDB-9rsx: Structure of RACK1 bound to the C-terminus of SERBP1 and the RIH region of ZAK 手法: EM (単粒子) / 解像度: 2.91 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-ZN: Unknown entry ChemComp-ANM: ANISOMYCIN / アニソマイシン / 抗生剤*YM
由来	homo sapiens (ヒト)
キーワード	RIBOSOME / ZAK / collision / RSR / quality control