Structural analysis of TRIM family PRYSPRY domains and its implications for E3-ligand design.

ABSTRACT: Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of RING-type E3 ubiquitin ligases and are attractive targets for the development of novel degraders that exploit the ubiquitin-proteasome pathway. More than half of all TRIM family members contain a PRYSPRY domain, a potentially druggable protein interaction module, located in their C-terminal region. Here, we have determined crystal structures of the PRYSPRY domains from nine TRIM family proteins: TRIM1 (MID2), TRIM9, TRIM10, TRIM11, TRIM15, TRIM16, TRIM18 (MID1), TRIM36, and TRIM67. These structures reveal conservation of the overall β-sandwich topology, despite low sequence conservation, with a unique subdomain swap observed in TRIM11. Significant variations were found in the loops flanking the canonical substrat

SUBMITTER: Zhubi R 

PROVIDER: S-EPMC12355088 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature