Dan Grabarczyk

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.

Filament formation and NAD processing by noncanonical human FAM118 sirtuins Nature Structural & Molecular Biology - Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that...

Very happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.

Degrons and degradation signals beyond short linear motifs - Nature Chemical Biology Degrons are degradation signals in target proteins to direct recognition and degradation by the ubiquitin–proteasome system. Wang et al. introduce degrons of different types, with an emphasis on high-...

A new Review discusses how degrons of different types, with an emphasis on high-order structural ones, regulate substrate-E3 interactions and how their dysregulation is linked to human diseases

www.nature.com/articles/s41...

An Asgard archaeon with internal membrane compartments

Brilliant study led by @fmacleod.bsky.social and Andriko von Kügelgen. Tight collaboration with @buzzbaum.bsky.social and lab. Congrats to all authors!

www.biorxiv.org/content/10.1...

📢 Open Call! The Max Perutz Labs invite applications for a Full Professorship in Integrative Structure Biology with a focus on in situ structural biology using cryo-electron tomography (cryo-ET) and related methods. More details ➡️ tinyurl.com/brswbymu

Split-site ubiquitination gives ZNFX1 new power in RNA defense Recent work by Grabarczyk et al. uncovers the molecular mechanism by which ZNFX1, an interferon-stimulated gene, employs a novel split-site E3 ligase domain structure to ubiquitinate both protein lysi...

Split-site ubiquitination gives ZNFX1 new power in RNA defense @cellcellpress.bsky.social
www.cell.com/molecular-ce...
www.sciencedirect.com/science/arti...

Elaborate machinery for inserting proteins into the outer membrane of bacteria Bacteria in the gut use an unusual molecular apparatus to insert complex proteins into their outer membrane.

Elaborate machinery for inserting proteins into the outer membrane of bacteria www.nature.com/articles/d41...

Structure and substrate recognition by the Twin-arginine translocation (Tat) pathway core complex https://www.biorxiv.org/content/10.1101/2025.09.18.677151v1

Dimerization for activation - Nature Chemical Biology Nature Chemical Biology - Dimerization for activation

Thanks a lot to Yiyun Song @natchembio.nature.com for highlighting our ZNFX1 paper. www.nature.com/articles/s41...

We have an open post-doc position in my group to study mRNA cleavage and polyadenylation using biochemical reconstitution and cryoEM.

Please get in touch if you are interested in joining this amazing team! 🔬🧬🤩
#RNA #cryoEM

I am excited to share our new preprint on the CAGE complex, a mysterious hollow protein complex that I first saw years ago while surveying Tetrahymena ciliary lysate www.biorxiv.org/content/10.1... #cilia #protistsonsky 🧬🧪

I am excited to announce that I will be moving to IMB Mainz next year! The Winter call for the IPP PhD program is now open; if you are interested in maternal #mRNA regulation and #translation in early vertebrate development, please apply! Deadline: 16 October.

More info: www.imb.de/students-pos...

ZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNA The detection of viral RNA inside cells triggers a diverse range of antiviral responses, including global translation inhibition, interferon secretion and RNA sequestration. Mutations in the gene ZNFX...

Pre-print: our description of RZ affiliate ZNFX1 is now online.

On binding viral RNA, ZNFX1 generates parallel Ub currents, coordinating Ub-dependent RNA silencing and aggregate resolution.

Huge effort from first authors Dan Squair and @eilidhrivers.bsky.social

www.biorxiv.org/content/10.1...

Inside the cell’s recycling hub: unveiling the architecture of UBR4 Researchers from the lab of Tim Clausen and collaborators have unveiled the three-dimensional structure of UBR4, a giant protein complex that safeguards cells by targeting defective proteins for destr...

Researchers around @clausenlab.bsky.social & @dangrabarczyk.bsky.social have unveiled the three-dimensional structure of UBR4, a giant protein complex that safeguards cells by targeting defective proteins for destruction—offering fresh insights into health & disease. www.science.org/doi/10.1126/...

We had great help from Hyun Kyu Song's lab who got crystal structures of substrate complexes, as well as our ongoing collaboration with the Manu Hegde lab. Also thanks to the efficient review process which really pushed us to improve the paper.

Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...

ZNFX1 compacts and tags RNA to keep immunity in check Tim Clausen’s lab at the IMP and collaborators have uncovered how the ancient immune protein ZNFX1 enables cells to walk the fine line between fighting infection and avoiding autoimmune damage. The te...

Scientists uncovered how the immune protein ZNFX1 enables cells to walk the fine line between fighting infection & avoiding autoimmune damage. ZNFX1 can ubiquitinate & compact host & viral RNA into molecular condensates, extending ubiquitin biology to RNA itself. More: www.imp.ac.at/news/article...

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles Grabarczyk et al. show the structure and mechanism of a non-canonical ubiquitin ligase, which is activated through nucleic-acid-induced oligomerization and is critical for cell survival during immune ...

Happy to share our work on the structure and function of the unusual E3 ligase ZNFX1 @cp-cell.bsky.social. It uses a nucleic acid-activated transthiolation mechanism, ubiquitinating and clustering RNA to protect cells in an immune response. @clausenlab.bsky.social
www.cell.com/cell/fulltex...

Opening for a biochemist to help us in the characterisation of novel ubiquitin-based antivirals. Diverse backgrounds welcomed; a keen sense of adventure is a must 😁

Details and criteria are below; please get in touch with any questions.

www.jobs.gla.ac.uk/job/research...

Covalently constrained ‘Di-Gembodies’ enable parallel structure solutions by cryo-EM - Nature Chemical Biology Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely...

Di-Gembodies (dimerized nanobodies) for improved and duplexed CryoEM of small and challenging targets!

A collaboration of @cmd.ox.ac.uk, STRUBI, @diamondlightsource.bsky.social, @rosfrankinst.bsky.social

Out now in Nature Chemical Biology @natchembio.nature.com

www.nature.com/articles/s41...

Structural basis for E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains - Nature Chemical Biology Tong et al. chemically trapped the structure of the E4 enzyme Ufd2, which mediates K48 branched ubiquitination on K29diUb and K29triUb, identifying Ufd2’s core region as a K29diUb binding domain and a...

A new paper reports the structure of the E4 enzyme Ufd2, which mediates K48 branched ubiquitination on K29diUb and K29triUb, identifying Ufd2’s core region as a K29diUb binding domain and a dimeric conformation for distal ubiquitin stabilization

www.nature.com/articles/s41...

Structures of dynamic interactors at native proteasomes by PhIX-MS and cryoelectron microscopy Proteasome function depends on a network of transient interactions that remain structurally and functionally unresolved. We developed PhIX-MS (Photo-induced In situ Crosslinking-Mass Spectrometry), a ...

‼️ Exciting new preprint from a close collaboration with Kylie Walters' group. Our study maps the binding sites of key regulators of the proteasome in situ.
www.biorxiv.org/content/10.1...

New preprint: In situ Architecture of #Plasmodesmata.

Using #cryoET, #AlphaFold & proteomics, we uncover the native organization of plant intercellular nanopores.

🔗 doi.org/10.1101/2025...

🧪🧵1/n
#teamtomo #PlantScience #Physcomitrium #Arabidopsis #cryoEM

🎉 Congratulations to our Daniel Grabarczyk, research associate in the Clausen lab, who has been awarded a prestigious FWF Principal Investigator Project Grant to support his research into the molecular mechanisms of innate immunity against viruses.

Read more: www.imp.ac.at/news/article...

In-cell discovery and characterization of a non-canonical bacterial protein translocation-folding complex Cryo-electron tomography has emerged as powerful technology for in-cell structural biology, and in combination with breakthroughs in protein structure prediction, offers a unique opportunity for illum...

This is just an excellent preprint by Rasmus Jensen and colleagues from Julia Mahamid's lab @embl.org - a tour de force of Cryogenic electron tomography to do in cell structural biology in which they discover a new complex and solve its structure and function! www.biorxiv.org/content/10.1...

ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213 - Nature Communications RNF213 is an E3 ligase with ATPase activity. Here, the authors show that RNF213 is activated by ATP binding and senses cellular energy states, and reveal a transthiolation mechanism induced by immune ...

Great to see this out. A story that spanned continents, cities and budget codes…

www.nature.com/articles/s41...

Big thanks to all the teams involved!

@clausenlab.bsky.social @e3chembio.bsky.social

Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination - Nature Communications The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how t...

Amazing chemical biology/structural biology work on K29/K48 branching E3 Ufd4/TRIP12 www.nature.com/articles/s41...

Thrilled to share the structure of dimerised human PINK1 docked to an endogenous translocase array on the mitochondrial surface, composed of two TOM complexes, bridged by a VDAC2 dimer! Published today in Science www.science.org/doi/10.1126/...

@wehi-research.bsky.social @komanderlab.bsky.social

Architecture of the 1.3 MDa complex of human UBR4 (2 x UBR4/KCMF1/CALM1). Picture shows top and side views of the cryo-EM density map and the modeled structure, colored by protein components and domains.

🎄 xmas preprint 🎄 we are excited to share our cryo-EM structure of UBR4 in complex with KCMF1 and CALM1. the PQC ligase forms a massive ubiquitination arena, primed to amplify ubiquitin chains (E4 activity) and boost degradation of defective proteins. www.biorxiv.org/content/10.1...

Happy to share our UBR4 structures. Check out the preprint to see how this giant E4 ligase complex selects substrates for ubiquitin chain extension. We also look at conservation and adaptations across humans, nematodes and plants.
www.biorxiv.org/content/10.1...
@clausenlab.bsky.social