Back

Intermolecular β-sheet formation guides the interaction between ubiquitin-like modifier FAT10 and adapter protein NUB1L

Weiss, C.; Catone, N.; Overall, S.; Barnes, A. B.; Aichem, A.; Groettrup, M.; Mathies, G.

2025-08-02 biochemistry
10.1101/2025.07.31.667942 bioRxiv
Show abstract

Under inflammatory conditions, the ubiquitin-like modifier FAT10 targets proteins for rapid and irreversible degradation by the 26S proteasome. FAT10 is degraded along with its substrates and in this process, the loose folding of FAT10 and adapter protein NUB1L have long been suspected to play crucial roles. We report here the investigation of the N-domain of FAT10 and its interaction with NUB1L by magic-angle spinning (MAS) NMR spectroscopy. A stretch of residues that is intrinsically disordered when the N-domain of FAT10 is in its ubiquitin-like {beta}-grasp fold, becomes part of a regularly structured loop and an intermolecular {beta}-sheet upon binding to NUB1L. The rest of the N-domain is now disordered, with exception of a series of anchor residues and the N-terminus. We propose that, in preparation of degradation by the proteasome, NUB1L stabilizes N-FAT10 in an unfolded state, acting as a holdase. The ability of FAT10 to interact in folded as well as unfolded form is essential for its role in inflammation-linked proteostasis.

Published in Journal of the American Chemical Society (predicted rank #1) · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.