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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

We made nanobodies that make your heart🫀 stop 🛑beating. Keep reading to learn how this taught us about how large membrane proteins like ion channels are folded and assembled in human cells. Beyond excited to share my lab's first preprint: Please 🔄 bit.ly/49A0PtD

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

Do you enjoy the thrill of discovery? Does this photo give you good vibes? Then you might be the right person to join our lab! Current projects range from chloroplast transcription to thylakoid membrane remodeling & we would be happy to welcome bright and motivated people at all career stages!

Our paper is now out in Science! Super excited to share our discovery that #mitochondria #pearling is the elusive mechanism driving the regular distribution and inheritance of #mtDNA nucleoids 🧬 [1/6]

The Landoni Lab opens this summer at UNIL! @fbm-unil.bsky.social 🔬 Quantitative #imaging + systems biology to decipher how #metabolic architecture & #mtDNA dynamically shape tissue development, #aging and #mitodisease. Beyond excited to fire up the lasers, open positions soon! 🧪 #mitochondria #newPI

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).

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...

Max Planck Institute of Biochemistry

Small molecules toggling the ubiquitin-proteasome system (UPS) are powerful regulators of protein degradation. Yet, mechanistic knowledge of how endogenous ligands gate UPS decisions remains rudimentary. Here, we define control of UPS access to Tryptophan-2,3-dioxygenase (TDO2), which converts the essential amino acid tryptophan (Trp) to N-formylkynurenine. When Trp concentrations are limiting, TDO2 is degraded to avert tryptophanemia. Using CRISPRi screening and biochemistry, we identify a CK2-FBXW11 kinase-E3 ligase cascade that generates and recognizes tandem TDO2 phosphodegrons when not protected by Trp. Trp binding to an exosite safeguards TDO2 from phosphorylation-dependent ubiquitylation. Effects of Trp analogs on CK2-FBXW11-dependent ubiquitylation indicated that the indole, amino, and carboxylate groups are necessary for substrate shielding. Cryo-EM reveals how these moieties order a region proximal to the phosphodegrons; without Trp, this segment is flexible, enabling phosphorylation-coupled ubiquitylation. Overall, our data uncovered an endogenous small molecule allosterically stabilizing its own metabolizing enzyme through protection from a phosphorylation-ubiquitylation cascade. ### Competing Interest Statement B.A.S. is a member of the scientific advisory boards of Proxygen and Lyterian. The other authors declare no competing interests. Max Planck Society, https://ror.org/01hhn8329 European Union, ERC AdvG, UPSmeetMet, 101098161 to BAS Boehringer Ingelheim Fonds, https://ror.org/00dkye506