9r11

Structure of the PRYSPRY domain of human MID2, crystal form II

spinqualitylabelsall models 9r11, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9r11 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.64Å Ligands: EDO, MPD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRIM1_HUMAN Publication Abstract from PubMed 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 beta-sandwich topology, despite low sequence conservation, with a unique subdomain swap observed in TRIM11. Significant variations were found in the loops flanking the canonical substrate-binding site, which modulate the shape and electrostatic properties of the binding pocket, hinting at substantial differences in substrate specificity and binding modes among family members. TRIM36 features a unique structural motif between the canonical beta-strands 2 and 3, leading to the formation of a dimer, with the canonical substrate-binding site partially occluded by the dimerization motif. In addition, we mapped the locations of missense mutations in MID1 associated with X-linked Opitz syndrome, suggesting that some of these mutations impair the conformational stability of the protein. Taken together, our data provide intriguing insights into the structural and functional divergence of TRIM family PRYSPRY domains, their potential druggability and substrate recognition, and the challenges of ligand design. Structural analysis of TRIM family PRYSPRY domains and its implications for E3-ligand design.,Zhubi R, Chaikuad A, Munoz Sosa CJ, Joerger AC, Knapp S J Struct Biol X. 2025 Jul 30;12:100134. doi: 10.1016/j.yjsbx.2025.100134. , eCollection 2025 Dec. PMID:40821731 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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