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/

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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