Special mention to @ammaraht.bsky.social, whose dedication to this project was instrumental to getting it here. Thanks to everyone across Leicester, FMI Basel, UCL and Geneva who contributed along the way.
www.biorxiv.org/content/10.6...
AlphaFold models of the human RNF20/RNF40 and S. cerevisiae Bre1 complexes show the same priming rearrangement, with conserved RBR residues. This looks like a universal activation mechanism for Bre1-type E3 ligases.
The interface is a short region in the HMD domain we call the RBR. Systematic mutagenesis in S. pombe produces accurately what the model predicts and is supported by the biochemistry.
The key finding: when we model HULC together with the HMD domain of Prf1, the RING domains and Rhp6 snap into a catalytically primed configuration. Without Prf1, the RMSD versus a known primed RING-E2-Ub structure is ~32 Å. With Prf1, it drops to 1.2 Å.
AF model of HULC
HULC is a 1:1:1:1 assembly (Brl1-Brl2-Rhp6-Shf1) built around an elongated coiled-coil hairpin. Shf1 is structurally integral to the hairpin—not peripheral. The complex is flexible, with its catalytic modules loosely tethered and poorly configured for ubiquitin transfer on their own.
H2Bub is deposited by the HULC complex, recruited to RNA Pol II via PAF1C. But how PAF1C activates HULC has been unclear. We used AlphaFold modelling, biochemical reconstitution, XL-MS, SAXS and cryo-EM to find out.
🧵 New preprint from our group, in collaboration with the @marcbuhler.bsky.social lab at FMI Basel and the Thalassinos lab at UCL. A long project and a finding we're really pleased with. Thread 👇
www.biorxiv.org/content/10.6...
Congratulations to the Chloe Hall and the Chaplin group! We're very proud to be part of this fantastic effort to produce structures of NHEJ assemblies on nucleosomes. This brings us closer to understanding how DNA repair machinery deals with a chromatin substrate: www.nature.com/articles/s41...
Please RS/RT. #GordonConference "Histone and DNA Modifications" Program is now online 🍾 #epigenetics #chromatin #histones 20.-25. July. Il Ciocco 🇮🇹
Register now: ➡️ shorturl.at/AtAjz
Exciting speaker lineup, many slots for talks selected from abstracts
🧬 1/ Heterochromatin protein 1 (HP1) still surprises us after all these years: It simply sticks to chromatin when pericentric heterochromatin domains – the chromocenters – are activated in mouse fibroblasts and acts as a local rather than global repressor. New preprint: doi.org/10.1101/2024...
I am recruiting a postdoc with experience in Protein Biochemistry, Structural Biology & Chromatin Biology. If you are passionate about the complex world of chromatin modifications, please contact me for more details 🙏.
Location: SAiGENCI, Adelaide, Australia
🦘🍷🏄🏖️🇦🇺
📢 #PhD Position 🎓 @leicstructbio.bsky.social @mcbleicester.bsky.social. Developing protein-based therapies for mesothelioma. Work with experts in epigenetics & cancer biology. Apply by Jan 10, 2025. #PhDSky #AcademicSky
Details: www.schalchlab.org/mesoinject
Please add me. Thank you.
We have an exciting and multidisciplinary fully-funded BBSRC MIBTP #PhD position between my lab and Massimo Cavallaro's lab coupling genomics, transcriptomics, and mathematical modelling to investigate the regulation of gene expression.
Deadline: 16th January 2025.
www.findaphd.com/phds/project...
🎓 Exciting #PhD opportunity in our lab at @mcbleicester.bsky.social and @leicstructbio.bsky.social. Join the BBSRC-funded MIBTP programme for a 4-year fully funded studentship with comprehensive training in year 1 + research project years 2-4. #PhDSky
#AcademicSky Details: tinyurl.com/4fhavzxh
Gutting when you find your dream project done and dusted on bioRxiv. Du et al. performed an impressive tour-de-force to solve the Clr4-H3K14ub structure. Great to see that the ubiquitin-binding region we found by XDS-MS matches the crystal structure perfectly! www.biorxiv.org/content/10.1...
Putting together packs of transcription and Chromatin people - Nominate others to add! go.bsky.app/5zgpZfg
In-cell structure and snapshots of copia retrotransposons in intact tissue by cryo-electron tomography www.biorxiv.org/content/10.1101/2024.02....