Work

Intermolecular β-sheet Formation Guides the Interaction between Ubiquitin-like Modifier FAT10 and Adapter Protein NUB1L

Year: 2026

Type: article

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 β-grasp fold, becomes part of a regularly structured loop and an intermolecular β-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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.6c05291

Authors: Charlotte Weiss, Sarah Overall, Nicola Catone, Alexander B. Barnes, Annette Aichem, Guinevere Mathies

Institutions: University of Konstanz, ETH Zurich, Institute of Cell Biology and Immunology Thurgau, Institute of Molecular Physical Science

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: National Science Foundation, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Konstanz