Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	ZAK activation at the collided ribosome.
Journal, issue, pages	Nature, Year 2025
Publish date	Nov 19, 2025
Authors	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 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. ...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.
External links	Nature / PubMed:41261136
Methods	EM (single particle)
Resolution	2.2 - 3.0 Å
Structure data	EMDB-54140: Cryo-EM map of the stalled 80S from the ZAK-bound human disome Method: EM (single particle) / Resolution: 2.35 Å EMDB-54141: Cryo-EM map of the collided 80S from the ZAK-bound human disome Method: EM (single particle) / Resolution: 2.35 Å EMDB-54147: Local refined map focusing on ZAK-RACK1 of the collided 80S Method: EM (single particle) / Resolution: 2.5 Å EMDB-54148: Local refined cryo-EM map focusing on ZAK-RACK1 of the stalled 80S Method: EM (single particle) / Resolution: 3.0 Å EMDB-54149: Cryo-EM map of the hybrid state translating 80S Method: EM (single particle) / Resolution: 2.2 Å EMDB-54150: Cryo-EM map of the hibernating 80S Method: EM (single particle) / Resolution: 2.6 Å EMDB-54165: Cryo-EM map of reconstituted ZAK-RBR-40S Method: EM (single particle) / Resolution: 2.3 Å EMDB-54166: Cryo-EM map of the stalled 80S from ZAK-K394D-disome Method: EM (single particle) / Resolution: 2.95 Å EMDB-54167: Cryo-EM map of the collided 80S from ZAK-K394D-disome Method: EM (single particle) / Resolution: 2.95 Å 54172 9rpv EMDB-54172, PDB-9rpv: Structure of the ZAK-bound human disome Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 2.91 Å
Chemicals	ChemComp-MG: Unknown entry ChemComp-ZN: Unknown entry ChemComp-ANM: ANISOMYCIN
Source	homo sapiens (human)
Keywords	RIBOSOME / ZAK / collision / RSR / quality control