SAVE THE DATE!
The EMBO workshop "Ubiquitin and Ubiquitin-like proteins in Health and Disease" will be on September 2026.
Exciting line up of talks and an amazing location!
Organised by @kulathu.bsky.social, @merbllab.bsky.social, @simonapolo.bsky.social, Claudio Joazeiro.
Registration open soon.
Exciting @biorxivpreprint.bsky.social by the groups of @pjcossar.bsky.social and @alessiociulli.bsky.social. They use a molecular glue between 14-3-3 and an intrinsically disordered domain of ERα to develop a molecular glue-based PROTAC recruiting VHL. doi.org/10.1101/2025...
#TPD #ChemSky #ChemBio
Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design www.biorxiv.org/content/10.1101/2025.11.17.688825v1 #cryoEM
Thank you for sharing @stephanhacker2.bsky.social!
An absolute pleasure to work with all co-authors on this study: from @alessiociulli.bsky.social’s lab (the 🤝 House of VHL 🤝) @alesalerno.bsky.social & Gajanan Sathe – and our wonderful collaboration Graham Marsh and Hannah Maple from Tocris Bio-Techne
We combined cryo-EM, chemical design & synthesis, ternary complex and ubiquitination biophysics & biochemistry, and cellular profiling to tease out the mechanisms at play.
Tuning linker rigidity and length determines whether a ternary complex orientation leads to:
- Efficient substrate ubiquitination & degradation,
- Partial or inefficient ubiquitination,
- Or complete stabilization through a locked, non-productive geometry.
From degradation to stabilisation!
Reprogramming the VHL-degrader CM11 into VHL-stabilisers through linker design, locking a non-ubiquitinable ternary complex.
🔗https://www.biorxiv.org/content/10.1101/2025.11.18.689129v1.full.pdf
Excited to see how this MGPROTAC concept evolves and what new disordered targets we can take on next!
Huge well done to our co-first author Carlo Verhoef and all our fantastic co-investigators Mark Nakasone, Aitana DeLaCuadraBaste, Tessa Harzing, Naomi Span, Gajanan Sathe, Kentaro Iso, Christian Ottmann, Luc Brunsveld and - last but not least @alessiociulli.bsky.social & Peter Cossar
We developed molecular glue-based PROTACs (MGPROTACs) that bring together ERα, 14-3-3 and the VHL E3 ligase in a quaternary complex, mediating ubiquitination on ERα and 14-3-3.
So pleased to contribute some cryo-EM and ubiquitination fun to this study
House of VHL meets house of 14-3-3 🤝
Presenting our study “Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design”
🔗https://www.biorxiv.org/content/10.1101/2025.11.17.688825v1
After the Krios I's 10-year birthday earlier this year (full story can be found here: lnkd.in/eCKF3vBF), it was awesome to visit the eBIC facilities at @diamondlightsource.bsky.social and see that the epic party hat still lives on 🥳
My first 🦋 post! Awesome view over the haar (fog) over the river Tay yesterday afternoon, on the train heading down to
@diamondlightsource.bsky.social for the CCP-EM Icknield workshop - looking forward to a great week of cryo-EM data processing and model building 🔬
