🎄 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... - ThreadSky

clausenlab.bsky.social • 67 days ago

🎄 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. https://www.biorxiv.org/content/10.1101/2024.12.18.629163v1

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clausenlab.bsky.social•67 days ago

complex structure, complex E4 mechanism – key features include a multivalent substrate-binding platform, a mediator arranging ubiquitin units for chain extension, and a molecular gatekeeper selecting PQC substrates while blocking functional proteins.

clausenlab.bsky.social•67 days ago

evolutionary conserved E4 complex – the core structure is conserved across eukaryotes, while species-specific adaptations allow operation in distinct cellular environments. and a BIG bonus: we unmask DI19 to be the enigmatic cofactor in plants.

clausenlab.bsky.social•67 days ago

E3/E4 giants – UBR4 complexes join the lineup of ubiquitination mega-enzymes, optimized to target diverse PQC substrates via an array of receptor sites, artfully arranged in ring-shaped protein scaffolds.

clausenlab.bsky.social•67 days ago

big thanks and kudos 👏 this work is the magnum opus of Dan Grabarczyk (@dangrabarczyk.bsky.social), made possible by a great collaboration with the labs of Manu Hegde (MRC-LMB) and Gus Versteeg (Vienna Biocenter).

aaryakat.bsky.social•67 days ago

Wow, megadalton protein complexes are crazy!

My proteins are ~100Kd usually so this is like seeing the mothership 🤩

msuskiewicz.bsky.social•67 days ago

Congratulations @clausenlab.bsky.social , @dangrabarczyk.bsky.social , and all authors!

leokiss.bsky.social•50 days ago

Wow, congrats on this massive Xmas present!

clausenlab.bsky.social•44 days ago

many thanks, leo! hope we can soon catchup.

leokiss.bsky.social•44 days ago

Me too! Already looking forward to it!

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