9IUN

Crystal structure of Trim25 Pspry

Summary for 9IUN

• Entry DOI: 10.2210/pdb9iun/pdb
• Descriptor: E3 ubiquitin/ISG15 ligase TRIM25 (2 entities in total)
• Functional Keywords: trim25, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 282901.52

Authors

Li, Y.L.,Lin, T.W. (deposition date: 2024-07-22, release date: 2025-07-30, Last modification date: 2026-08-12)

Primary citation

Li, Y.,Wu, S.,Tian, X.,Kong, C.,Hong, W.,Xiao, T.,Wang, S.,Wei, Z.,Su, Z.,Ren, H.,Song, Y.,Hu, L.,Lin, D.,Yao, H.,Han, J.,Chen, X.,Lin, T.
The structural basis of TRIM25-mediated regulation of RIG-I.
J.Biol.Chem., 301:108367-108367, 2025

PubMed Abstract: TRIM25, an E3 ligase, is an important regulator to modulate the functions of retinoic acid inducible gene-I (RIG-I) and other factors in innate immunity. Herein the structural interaction between the 2CARD domain of RIG-I and the PRYSPRY domain of TRIM25 was investigated by NMR, X-ray crystallography, computer-assisted modeling, and cell-based assays to elucidate the complex structure of PRYSPRY/2CARD. The interacting model indicated that docking of 2CARD onto PRYSPRY brought two RIG-I molecules into a close proximity to form a dimer. The attachment of a short ubiquitin chain covalently by the TRIM25's E3 ligase activity was favorable for tethering a neighboring RIG-I dimer to form the tetrameric RIG-I by noncovalent interactions. The data supported the notion that the TRIM25-RIG-I interaction was important to activate the RIG-I pathway to suppress the replication of RNA viruses, such as vesicular stomatitis virus. This work provides a structural rationale to delineate the underlying mechanism of TRIM25 regulation of RIG-I.

PubMed: 40024477
DOI: 10.1016/j.jbc.2025.108367

Experimental method

X-RAY DIFFRACTION (2.698 Å)