Molecular basis for ubiquitin/Fubi cross-reactivity in USP16 and USP36.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
04
01
2023
accepted:
21
06
2023
medline:
30
10
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Ubiquitin and ubiquitin-like proteins typically use distinct machineries to facilitate diverse functions. The immunosuppressive ubiquitin-like protein Fubi is synthesized as an N-terminal fusion to a ribosomal protein (Fubi-S30). Its proteolytic maturation by the nucleolar deubiquitinase USP36 is strictly required for translationally competent ribosomes. What endows USP36 with this activity, how Fubi is recognized and whether other Fubi proteases exist are unclear. Here, we report a chemical tool kit that facilitated the discovery of dual ubiquitin/Fubi cleavage activity in USP16 in addition to USP36 by chemoproteomics. Crystal structures of USP36 complexed with Fubi and ubiquitin uncover its substrate recognition mechanism and explain how other deubiquitinases are restricted from Fubi. Furthermore, we introduce Fubi C-terminal hydrolase measurements and reveal a synergistic role of USP16 in Fubi-S30 maturation. Our data highlight how ubiquitin/Fubi specificity is achieved in a subset of human deubiquitinases and open the door to a systematic investigation of the Fubi system.
Identifiants
pubmed: 37443395
doi: 10.1038/s41589-023-01388-1
pii: 10.1038/s41589-023-01388-1
pmc: PMC10611586
doi:
Substances chimiques
Ubiquitin
0
Ubiquitin Thiolesterase
EC 3.4.19.12
Ubiquitins
0
Endopeptidases
EC 3.4.-
USP16 protein, human
0
USP36 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1394-1405Subventions
Organisme : Max-Planck-Gesellschaft (Max Planck Society)
ID : CGC-III-352S
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 424228829 - SFB1430
Informations de copyright
© 2023. The Author(s).
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