ArticleNature structural & molecular biology2025
NUB1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed.
- Structural determinants for FAT10 activation and transfer from UBA6 to E2 enzymes.Nature communications · 2026Article
- Co-sedimentation is the key to the structural investigation of wild-type FAT10.Journal of biomolecular NMR · 2026Article
- Identifying endogenous substrates of the 26S proteasome through site-specific photocrosslinking.bioRxiv : the preprint server for biology · 2026Article
- Molecular basis of ubiquitin-independent recognition and degradation of ODC/Antizyme by the 26S proteasome.bioRxiv : the preprint server for biology · 2026Article
- Intermolecular β-sheet Formation Guides the Interaction between Ubiquitin-like Modifier FAT10 and Adapter Protein NUB1L.Journal of the American Chemical Society · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Substrate-interacting pore loops of two ATPase subunits determine the degradation efficiency of the 26S proteasome.Nature communications · 2026Article
- Structures of the 26Science advances · 2026Article
- Structural landscape of the degrading 26S proteasome reveals conformation-specific binding of TXNL1.Nature structural & molecular biology · 2025Article
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation.Frontiers in immunology · 2025Article
- Phosphorylated FAT10 Is More Efficiently Conjugated to Substrates, Does Not Bind to NUB1L, and Does Not Alter Degradation by the Proteasome.Biomedicines · 2024Article
- Structural landscape of AAA+ ATPase motor states in the substrate-degrading human 26S proteasome reveals conformation-specific binding of TXNL1.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Update of
Authors and funding
8 authors.
Funding
Abstract
The ubiquitin-like modifier FAT10 targets hundreds of proteins in the mammalian immune system to the 26S proteasome for degradation. This degradation pathway requires the cofactor NUB1, yet the underlying mechanisms remain unknown. Here, we reconstituted a minimal in vitro system with human components and revealed that NUB1 uses the intrinsic instability of FAT10 to trap its N-terminal ubiquitin-like domain in an unfolded state and deliver it to the 26S proteasome for engagement, allowing the degradation of FAT10-ylated substrates in a ubiquitin-independent and p97-independent manner. Using hydrogen-deuterium exchange, structural modeling and site-directed mutagenesis, we identified the formation of an intricate complex with FAT10 that activates NUB1 for docking to the 26S proteasome, and our cryo-EM studies visualized the highly dynamic NUB1 complex bound to the proteasomal Rpn1 subunit during FAT10 delivery and the early stages of ATP-dependent degradation. These findings identified a previously unknown mode of cofactor-mediated, ubiquitin-independent substrate delivery to the 26S proteasome that relies on trapping partially unfolded states for engagement by the proteasomal ATPase motor.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.