Systematic discovery of motif-based interactions of the auxiliary domains of USP family deubiquitinases - PubMed
5 hours ago
- #Structural Biology
- #Protein Interactions
- #Deubiquitinases
- The study focuses on the ubiquitin-specific proteases (USPs) family, the largest group of human deubiquitinating enzymes (DUBs), which typically show polyubiquitin linkage-type agnosticism.
- Auxiliary domains (ADs) in USPs are hypothesized to bind short linear motifs (SLiMs) in intrinsically disordered protein regions for substrate targeting and complex assembly.
- Researchers systematically tested 29 USP-ADs and two full-length USPs for SLiM binding using proteomic-peptide phage display, peptide SPOT arrays, and affinity measurements.
- SLiM-based interactions were discovered for 14 ADs from 9 USP-DUBs, including CYLD, USP11, USP19, USP20, USP22, and USP33.
- The zf-UBP and DUSP2 domains of USP20 and USP33 were identified as SLiM binding ADs with similar profiles, explaining functional redundancy between these DUBs.
- Unique motifs recognized by auxiliary domains such as CAP-Gly, UBL, zf-UBP, and DUSP were revealed, with implications for substrate recognition and multiprotein complex formation.