The structural basis of TRIM25-mediated regulation of RIG-I
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.
Authors
- Hongwei Yao (ORCID: https://orcid.org/0000-0003-3995-6520)
- Lichen Hu (ORCID: https://orcid.org/0009-0003-3444-5809)
- Wenbin Hong (ORCID: https://orcid.org/0000-0001-6002-5726)
- Tianyichen Xiao
- Zhiming Su (ORCID: https://orcid.org/0000-0001-9116-0365)
- Zhiming Wei (ORCID: https://orcid.org/0000-0002-9215-7149)
- Yunlong Li
- Xueqin Chen (ORCID: https://orcid.org/0000-0002-1828-1985)
- Donghai Lin (ORCID: https://orcid.org/0000-0002-2318-2033)
- Kong Chen (ORCID: https://orcid.org/0000-0001-6980-5454)
- Haixia Ren
- Xuyang Tian (ORCID: https://orcid.org/0009-0009-9605-6626)
- Tianwei Lin (ORCID: https://orcid.org/0000-0002-9293-4673)
- Songqing Wang (ORCID: https://orcid.org/0009-0006-8887-9815)
- Siqi Wu
- Jiahuai Han
- Yunlong Song
Institutions
- Soochow University (TW)
- Xiamen University (CN)
- Soochow University (CN)
- First Affiliated Hospital of Xiamen University (CN)
- State Key Laboratory of Membrane Biology
- Tsinghua University (CN)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-02-28
- DOI
- https://doi.org/10.1016/j.jbc.2025.108367
- Citations
- 5
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 3.99
Funders
- Salt Science Research Foundation
- Chinese Academy of Sciences
- Xiamen University
- Shanghai Advanced Research Institute, Chinese Academy of Sciences