Title |
Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway
|
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Published in |
Cell Reports, July 2016
|
DOI | 10.1016/j.celrep.2016.06.070 |
Pubmed ID | |
Authors |
Jacint G. Sanchez, Jessica J. Chiang, Konstantin M.J. Sparrer, Steven L. Alam, Michael Chi, Marcin D. Roganowicz, Banumathi Sankaran, Michaela U. Gack, Owen Pornillos |
Abstract |
Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 33% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 101 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 27 | 27% |
Researcher | 23 | 23% |
Student > Bachelor | 13 | 13% |
Student > Master | 8 | 8% |
Student > Postgraduate | 4 | 4% |
Other | 7 | 7% |
Unknown | 19 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 36 | 36% |
Agricultural and Biological Sciences | 24 | 24% |
Immunology and Microbiology | 7 | 7% |
Chemistry | 6 | 6% |
Computer Science | 1 | <1% |
Other | 6 | 6% |
Unknown | 21 | 21% |