iiinova — where your digital self keeps evolving

Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 15/09/2026

Today, the day of the 100th anniversary symposium for Jean-Pierre Serre in Paris, I'm thinking of this quote from another mathematician, A. Connes. I do think it's important we foster confidence in our own expertise - as a nonsense filter and departure point for creativity.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 14/09/2026

General conclusions/models? Efficient SUMOylation as a new function of (some) BTB domains + it supports a hypothesis that structural SUMOylation motifs pre-organised for productive UBC9 engagement may be more efficiently modified than typical flexible SUMOylation motifs. Might apply to other PTMs.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 14/09/2026

This property extends to 5 human ZBTB proteins (38, 4, 33, 21, 14). This work continues from our previous study www.cell.com/molecular-ce... where we found that BTB domains of around 20 different ZBTB proteins form filaments. Now we show that 5 other ZBTB proteins undergo efficient SUMOylation.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 14/09/2026

Strikingly, the SUMOylation of ZBTB38 BTB is as efficient and complete under our conditions in vitro as that of RANGAP1, so far known as the best modified SUMO substrate. We can also detect endogenous modification of flZBTB38 in cells with western and show it depends on K43.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 14/09/2026

We found, in an AlphaFold interaction screen, the SUMO E2 UBC9 as a potential binder to BTB domain of ZBTB38. The predicted binding surface is conserved and positions K43 of ZBTB38 within UBC9 active site. We reconstituted & validated the interaction with SEC and ITC.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 07/09/2026

@inoagrafioti.bsky.social This I haven't read either (talking about books I haven't read...😳) but it's also on my shelf - Oxford women intellectual history one generation (two?) earlier.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 13/08/2026

Really cool systems with protein homomultimerisation at their cores. The authors say that these sort of proteins might function less like traditional transcription factors (which bind to specific loci and locally activate or repress) and more like architectural chromatin regulators akin to cohesin.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 13/08/2026

the DNA is doing much of the multimerisation work, and on the protein side the RBR, enriched in aromatic residues, adapts to form weak protein-protein contacts. It looks like this 🔽, with RBR in green.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 25/03/2026

Look at this: GATA1 levels in K562 extract are probed by WB after incubation with increasing concentrations of immobilised cognate or mutated DNAs. High DNA concentrations deplete the TF; with less DNA, more TF remains. Quantify to get binding curves with apparent Kd. Mutated DNA depletes less.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 18/03/2026

Going through mailbox and deleting spam conference and journal invitations be like...

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 18/03/2026

New photo of our research team has just dropped (with Sophia, our CNRS concours candidate, and Ambre, a visitor researcher, as guests). Not all members are there but most are, including some short-term interns. Very honoured to (try to) be a leader of this team.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 19/02/2026

One comment - it seems to me that the models where the Ub C-terminus is far from the catalytic Cys may represent Ub docked noncovalently on the E2 backside. Since most E2s can bind a second Ub there, compatible with the covalent Ub in a closed/open conformation...

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 08/01/2026

My phone is not very good but we did have quite a lot of snow until yesterday (@cbm-upr4301.bsky.social )

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 24/11/2025

We suggest defining four hydrophobic subpockets (HS1-HS4) on SUMO, each recognising one residue of the hydrophobic SIM core. In addition, we define the β strand-binding subpocket (βS) for binding the β-strand part of SIM, and the phospho/acidic-binding subpocket (PS) interacting with acidic part.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 05/11/2025

Our focus is on structural and evolutionary aspects. Which SUMO surfaces and residues mediate its different interactions? How is SUMO distinguished from ubiquitin to create a specific, orthogonal PTM system? What do the surface properties of SUMO imply for the evolution of its binders and function?

A) Regions involved in different interactions marked on a multiple-sequence alignment of SUMO proteins. B) Those regions indicated on a SUMO structure. *=SIM groove, **=Ile44 Ub patch

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 30/09/2025

A part of our team at the recent EMBO SUMO conference in La Grande Motte/Montpellier

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 05/06/2025

Very happy that our SIAH1 article - published online in February - was now chosen for the cover of the new issue of the @febsj.bsky.social . Thank you @spartelab.bsky.social for the wonderful collaboration and the lovely cellular images. febs.onlinelibrary.wiley.com/toc/17424658...

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 28/04/2025

PhD and postdoc positions with a brilliant friend of mine, Martin Lukačišin in Bratislava, Slovakia. Check out his website and papers lukacisinlab.github.io

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

This is a cover design that wasn't accepted, showing SIAH1 multimers on top of cells (SIAH1 red, actin green). We were not able to visualise SIAH1 chains in vitro, as we could only purify N- or C-term halves of SIAH1 separately: the blue chains are made from combined dimeric structures of each half.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

Lastly, Lucija performed nice in-vitro ubiquitylation assays showing that the V90R mutant of the RING-ZnF1 fragment is deficient in making long ubiquitin chains. So there is also a role for RING dimerisation in catalysing polyubiquitylation, as seen for other dimeric RING Ub E3s.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

When we look at the colocalisation with an aggregated substrate, Synphilin-1, SIAH1 WT does colocalise, but this is largely prevented when we block RING domain dimerisation with the V90R mutation. This leads us to a model where multimerisation allows high-avidity binding to multivalent substrates.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

Here's what happens in cells: mCherry-tagged SIAH1 (admittedly, somewhat overexpressed) localises to elongated clusters, but you need to have both RING and SBD for that, and no V90R mutation, otherwise SIAH1 is mostly diffuse.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

We crystallised & Franck solved the crystal structure of the dimer formed by the RING-ZnF1 part of SIAH1. We confirmed dimerisation in solution, & showed V90R mutation blocks RING dimerisation. @origichals.bsky.social did lovely AlphaFold modelling showing dimerisation across the SINA/SIAH family.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 06/02/2025

Happy to share our new study showing that the Ub E3 ligase SIAH1, known to dimerise via its C-term SBD, also dimerises via its N-term RING. When these tendencies combine, full-length SIAH1 forms multimers, which might explain its clustering in cells & preference for aggregated/multimeric substrates.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 16/11/2024

We are still considering postdoc candidates for the post advertised below. A 2-year contract beginning in 2025 to work on protein SUMO E3 ligases and the nucleosome.

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Marcin J. Suskiewicz @msuskiewicz.eurosky.social · 14/11/2024

A recent group photo on the banks of the Loiret ☀️

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