Share
))
HBO and The Ringer's Bill Simmons hosts the most downloaded sports podcast of all time, with a rotating crew of celebrities, athletes, and media staples, as well as mainstays like Cousin Sal, Joe House, and a slew of other friends and family members who always happen to be suspiciously available.
…
continue reading
Manage episode 520979303 series 3682575
Content provided by [email protected] (Gustavo Barra) and Gustavo Barra. All podcast content including episodes, graphics, and podcast descriptions are uploaded and provided directly by [email protected] (Gustavo Barra) and Gustavo Barra or their podcast platform partner. If you believe someone is using your copyrighted work without your permission, you can follow the process outlined here https://staging.podcastplayer.com/legal.
️ Episode 208: ZAK, Collided Ribosomes, and the Stress Switch
In this episode of PaperCast Base by Base, we explore how collided ribosomes activate the MAP3K ZAK to drive the ribotoxic stress response and shape cell fate decisions under translational stress.
Study Highlights:
Using biochemistry, cryo-electron microscopy and crosslinking-based RNA mapping, the authors define how ZAK is constitutively recruited to ribosomes and how this engagement changes upon stress-induced ribosome collisions. They show that ZAK contacts the 40S subunit through a C-terminal eS27 pin and rRNA patches and anchors to RACK1 via a RACK1-interacting helix, while a collision-sensitive FPxL-containing RACK1-interacting motif becomes engaged only when two ribosomes collide. Disome formation brings two RACK1 molecules into proximity, allowing ZAK SAM domains to dimerize across the collision interface and enabling kinase activation, with pathogenic and engineered SAM variants revealing how this interface tunes activity on and off the ribosome. The study also identifies the ribosome-binding protein SERBP1 as a negative regulator that competes with ZAK for the FPxL-binding site on RACK1, thereby preventing inappropriate activation during basal translation.
Conclusion:
This work provides a structural and mechanistic blueprint for how ribosome collisions are translated into ZAK kinase activation, offering new entry points to modulate stress signalling in disease contexts.
Music:
Enjoy the music based on this article at the end of the episode.
Reference:
Huso VL, Niu S, Catipovic MA, Saba JA, Denk T, Park E, Cheng J, Berninghausen O, Becker T, Green R, Beckmann R. ZAK activation at the collided ribosome. Nature. 2025. https://doi.org/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
Castos player https://basebybase.castos.com
Episode Slug: zak-collided-ribosome-stress-switch
On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.
211 episodes
