208: ZAK, Collided Ribosomes, and the Stress Switch

ZAK, Collided Ribosomes, and the Stress Switch Music:Enjoy the music based on this article at the end of the episode. DOI:10.1038/s41586-025-09772-8 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/zak-collided-ribosomes-and-the-stress-switch ️ Episode:208: ZAK, Collided Ribosomes, and the Stress Switch ️ Season:1 Article title:ZAK activation at the collided ribosome Journal:Nature QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-24. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited sections covering ZAK constitutive ribosome binding, collision sensing via RACK1, RIH and RIM motifs, SAM-domain dimerization as activation switch, SERBP1 regulation, CLIP-seq mapping to ES7/ES6b/c, and downstream MAPK signaling.- transcript topics: RSR overview and ZAK as central kinase; Constitutive ribosome binding of ZAK to the 40S via pin and ES7-patch; Collision interface: RACK1, RIH, and RIM motifs; SAM-domain dimerization as activation switch; SERBP1 competition at FPxL motif on RACK1; CLIP-seq mapping ES7 and ES6b/c on 18S rRNA QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- ZAK activation is triggered by ribosome collisions via SAM-domain dimerization at the collision interface.- RACK1 acts as the collision scaffold bridging ZAK to both collided ribosomes, with ZAK interacting through RIH and RIM motifs.- RIH anchors ZAK to RACK1 and is necessary for binding and activation.- FPxL motif (RIM) is strictly required for ZAK activation on collided ribosomes, but not for initial binding.- SERBP1 competes for the RACK1 FPxL binding site and acts as a negative regulator of ZAK activation.- ZAK pin (eS27-pin) anchors ZAK to the 40S subunit via W768; ES7-patch also contributes to ribosome binding. QC result: Pass. Chapters (00:00:00) - The cell's ribotoxic stress response(00:05:10) - The Rack 1 Collapse Sensor(00:09:55) - How does the ZK SAM domains dimerize to trigger cell(00:12:16) - When We Collide