Aniruddha Das

How does the cell tune p97/Cdc48 activity for different substrates?
Study suggests different adaptor combinations function as molecular accelerators of protein clearance.

www.science.org/doi/10.1126/...

Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress Cryo–electron tomography reveals how mitochondria reorganize their translation and folding systems under proteostatic stress.

Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress

www.science.org/doi/10.1126/...

M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress - Cell Death & Differentiation Cell Death & Differentiation - M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress

More evidence that LUBAC has functions beyond inflammation: Our study shows that LUBAC regulates AMPK signalling to control metabolic adaptation, autophagy, and cell death. This might explain the metabolic problems observed in LUBAC deficiency and ORAS patients. www.nature.com/articles/s41...

Degrons and degradation signals beyond short linear motifs - Nature Chemical Biology Degrons are degradation signals in target proteins to direct recognition and degradation by the ubiquitin–proteasome system. Wang et al. introduce degrons of different types, with an emphasis on high-...

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

FAF1 and FAF2 enhance human p97-UFD1-NPL4 complex unfoldase activity enabling rational design of p97 activators https://www.biorxiv.org/content/10.64898/2026.02.24.707758v1

This project started with confusion 🤔 www.nature.com/articles/s41...

Loss of LUBAC or OTULIN causes severe inflammatory disease. But patients also show clear metabolic defects.

Neither LUBAC nor OTULIN had been linked to metabolic regulation.

So where do these metabolic manifestations come from?

🧐 What if metabolic defects are not just a consequence of inflammatory disease - but actively contribute to it?

Inflammation and metabolism are deeply intertwined, but the molecular links remain unclear.

Our new paper in Cell Death & Differentiation uncovers one. 🧵👇
nature.com/articles/s41...

This is a video summarizing our recent paper (www.nature.com/articles/s41...)

youtu.be/eNY2CRlYTRo

FEBS Press Cells rely on regulated proteostasis mechanisms to keep their internal compartments functioning properly. When these mechanisms fail, damaged proteins accumulate, disrupting organelles, such as the n....

Our new review on proteostasis of organelles in aging & disease is now online in The FEBS Journal!
We discuss recent insights on how #proteostasis safeguards organelle integrity and function across the cell in #aging and disease
doi.org/10.1111/febs...

David's AlphaFold WorkShop 2026 YouTube video by David Fay

Greetings! I decided to make a YouTube video of my AlphaFold workshop that I've given a few times in the past year. Caveats aside, people seem to find this useful for thinking about how to model protein interactions and how to interpret various AF outputs 1/2

www.youtube.com/watch?v=u63o...

MoSAIC: An Integrated and Modular Workflow for Confident Analysis of Protein Post-Translational Modification Landscapes Investigating multiple protein post-translational modifications (PTMs) is critical for unraveling the complexities of protein regulation and the dynamic interplay among PTMs, a growing focus in proteo...

MoSAIC: An Integrated and Modular Workflow for Confident Analysis of Protein Post-Translational Modification Landscapes #MCP www.mcponline.org/article/S153...

We are thrilled to share our new pre-print on the molecular anatomy of nuclear proteasome in human sperm cells! #In-cellcryo-ET + #SPA + #LM! @piotrkolata.bsky.social @a-dsantos.bsky.social, @tomdendooven.bsky.social!! doi.org/10.64898/202...

UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6 Nature Structural & Molecular Biology - Riechmann et al. uncover structural features governing ubiquitin transfer from ubiquitin-activating E1 enzymes UBA1 and UBA6 to specific E2...

Excited to share our work into ubiquitin E1-E2 specificity mechanisms. CryoEM visualising #ubiquitin transfer,biochemistry,evolution @labhofmann.bsky.social & tissue expression analyses @psarkies.bsky.social Big thanks to the team,reviewers & handling editor @dimitristypas.bsky.social rdcu.be/eTRdR

Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer ...

Induced ubiquitination of the partially disordered Estrogen Receptor alpha protein via a 14-3-3-directed molecular glue-based PROTAC design

Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import. rupress.org/jcb/article/...

Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation Heterobifunctional proteolysis-targeting chimeras (PROTACs) have emerged as a powerful strategy to degrade disease-relevant proteins, enabling targeting of previously "undruggable" proteins. Current d...

New preprint out! We show that PROTAC-induced ubiquitination can bypass canonical ERAD to degrade ER membrane proteins. Wonderful collaboration w/ @dannomura.bsky.social and huge credit to grad student superstar Sydney Tomlinson!
www.biorxiv.org/content/10.1...

We’ve made some new tools to manipulate N-recognins. Check them out in our preprint.
www.biorxiv.org/content/10.1...

ZAK activation at the collided ribosome - Nature The kinase ZAK is activated at collided ribosomes to mediate the ribotoxic stress response.

Check out our latest work on how collided ribosomes activate the MAP3K ZAK! 💫

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

A fun collaboration with @beckmannlab.bsky.social @doubleshuang.bsky.social

Degrons and degradation signals beyond short linear motifs - Nature Chemical Biology Degrons are degradation signals in target proteins to direct recognition and degradation by the ubiquitin–proteasome system. Wang et al. introduce degrons of different types, with an emphasis on high-...

A new Review discusses how degrons of different types, with an emphasis on high-order structural ones, regulate substrate-E3 interactions and how their dysregulation is linked to human diseases

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

MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.

Or from a single dish of HEK cell culture in the case of two membrane proteins.

Out in Nature Methods now! lnkd.in/gpyBSceg

Wonderful collaboration with the Efremov lab.

Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration - Nature Cell Biology Li et al. uncover a connection between metabolic cues and mitochondrial protein degradation, showing that specifically leucine stabilizes outer mitochondrial membrane proteins by inhibiting ubiquityla...

Very interesting work by Hoppe group. Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration | Nature Cell Biology share.google/0GpbVUCmqJ8Q...

Structure of the TXNL1-bound proteasome Nature Structural & Molecular Biology, Published online: 06 August 2025; doi:10.1038/s41594-025-01639-wGao, Nardone et al. report the cryo-EM structure of human TXNL1 bound to the proteasome and reveal interactions required for the stress-induced degradation of TXNL1, an abundant protein that may regulate proteasomal activity.

New online: Structure of the TXNL1-bound proteasome

The E3 ligase Parkin ubiquitinates many proteins. Koszela, Walden (@hw1o9.bsky.social) et al. @uofglasgow.bsky.social‬ identify and biochemically validate a direct Parkin interaction with a substrate, Miro1. rupress.org/jcb/article/...

Inhibition of peroxisomal protein PRX-11 promotes longevity in Caenorhabditis elegans via enhancements to mitochondria Peroxisomes execute essential functions in cells, including detoxification and lipid oxidation. Despite their centrality to cell biology, the relevance of peroxisomes to aging remains understudied. We...

Inhibition of peroxisomal protein PRX-11 promotes longevity in Caenorhabditis elegans via enhancements to mitochondria www.biorxiv.org/content/10.1...

The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control The noncanonical translation initiation factor eIF2A plays critical roles in diverse cellular processes, including the integrated stress response, neurodegeneration and tumorigenesis. However, the pre...

Identified in the 1970s, the precise molecular function of the alternative initiation factor eIF2A has remained unclear. Here, we map its interactome and uncover a surprising role in ribosome-associated quality control (RQC) upon ribosome stalling. 1/x

www.biorxiv.org/content/10.1...

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

1/
New preprint!
How do transcription factors (TFs) use intrinsically disordered regions (IDRs) to find their target sites?

www.biorxiv.org/content/10.1...
#TranscriptionFactors #IDPs #SingleMolecule #Biophysics

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...

Single-molecule analysis reveals the mechanism of chromatin ubiquitylation by variant PRC1 complexes Single-molecule experiments show that active conformation formation controls chromatin ubiquitylation kinetics by variant PRC1.

Our new study of chromatin ubiquitylation by variant PRC1 on the single-molecule scale: We visualize directly how vPRC1 ubiquitylates neighboring nucleosomes during a single binding event, showing a potential mechanism how H2Aub domains are established.
www.science.org/doi/10.1126/...

Excited that our work revealing the structure and function of the monster stress response silencing factor, the E3 ligase SIFI, is now out! Congratulations to the most amazing team of Zhi Yang, Diane Haakonsen, Michael Heider and Sam Witus!

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

Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination - Nature Communications The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how t...

Amazing chemical biology/structural biology work on K29/K48 branching E3 Ufd4/TRIP12 www.nature.com/articles/s41...