The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation (TDMD) is now published! 🎉🍾 We, @bartellab.bsky.social and Schulman lab, describe how 2-RNA factors control protein degradation by recruiting an E3 ligase. @mpibiochem.bsky.social
www.nature.com/articles/s41...

Formation & function of #MembranelessOrganelles! #CryoET structures of #proteasome storage granules inside cells!
Read our paper @cp-cell.bsky.social!

❕Publication: doi.org/10.1016/j.ce...
❕Press Release: www.biochem.mpg.de/en/pressroom

@uoftmedicine.bsky.social
@erc.europa.eu #UPSmeetMet

Many thanks to Brenda, Basti, all co-authors @mpibiochem.bsky.social and collaborators Simon and Benoît @ludwigcancer.bsky.social!

6/6

Occupation of an enzyme exosite to regulate accessability of a phosphodegron to a kinase-E3 ligase cascade is a new mechanism of metabolite-gated protein degradation.

5/6

SAR studies with Trp analogs reveal that only Trp and its synthetic anlog α-methyl Trp, inhibit degron accessibility by structuring a C-terminal region.
This links ligand chemistry to decision-making by the UPS.

4/6

When Trp is limiting, TDO2 is subject to proteasomal degradation to avert tryptophanemia.
By combining CRISPRi screening, biochemistry and cryo-EM, we discovered how Trp is perceived by binding to an exosite on TDO2 to control its phosphorylation-dependent ubiquitylation.

3/6

Since the 1950s, long before the discovery of the ubiquitin-proteasome system, Tryptophan 2,3-dioxygenase (TDO2) emerged as a model for protein stability – a mystery now solved!

2/6

New year, new preprint! 🎊

We are excited to share our recent work on #E3 ligase regulation in #metabolism!

www.biorxiv.org/content/10.6...

#ubiquitin #targetedproteindegradation #chemicalbiology

1/6

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains - Nature Structural & Molecular Biology Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation sha...

Excited to share our latest study on how K29/K48-branched #ubiquitin chains are forged by the #E3 ligase TRIP12, and how this suggests a consensus mechanism for chain formation by HECT E3s!

@natsmb.nature.com

1/7

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

UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains Ubiquitin chains determine the fates of their modified proteins, including proteasomal degradation. Kiss et al. present UbiREAD, a technology to monitor cellular degradation and deubiquitination at hi...

Super excited to share our latest work on deciphering the #Ubiquitin Code

“𝗨𝗯𝗶𝗥𝗘𝗔𝗗 𝗱𝗲𝗰𝗶𝗽𝗵𝗲𝗿𝘀 𝗽𝗿𝗼𝘁𝗲𝗮𝘀𝗼𝗺𝗮𝗹 𝗱𝗲𝗴𝗿𝗮𝗱𝗮𝘁𝗶𝗼𝗻 𝗰𝗼𝗱𝗲 𝗼𝗳 𝗵𝗼𝗺𝗼𝘁𝘆𝗽𝗶𝗰 𝗮𝗻𝗱 𝗯𝗿𝗮𝗻𝗰𝗵𝗲𝗱 𝗞48 𝗮𝗻𝗱 𝗞63 𝘂𝗯𝗶𝗾𝘂𝗶𝘁𝗶𝗻 𝗰𝗵𝗮𝗶𝗻𝘀”

@cp-molcell.bsky.social

1/8

www.cell.com/molecular-ce...