iiinova — where your digital self keeps evolving

Reposted by Charlotte Crowe

Rachel O'Dea @rnidhea.bsky.social · 08/12/2025

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.

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Reposted by Charlotte Crowe

cryoEM papers @cryoempapers.bsky.social · 18/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

We combined cryo-EM, chemical design & synthesis, ternary complex and ubiquitination biophysics & biochemistry, and cellular profiling to tease out the mechanisms at play.

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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.

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

Excited to see how this MGPROTAC concept evolves and what new disordered targets we can take on next!

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 19/11/2025

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

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Charlotte Crowe @charlcrowe.bsky.social · 15/10/2025

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 🥳

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Charlotte Crowe @charlcrowe.bsky.social · 13/10/2025

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 🔬

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