ALBERT

Description: Publication date: Available online 14 July 2016 Source: Cell Reports Author(s): 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 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. Graphical abstract Teaser Sanchez et al. elucidate the structural requirements for TRIM25 catalytic activation and its effector functions in the antiviral RIG-I pathway. Higher-order oligomerization of TRIM25 is promoted by RIG-I and likely constitutes a regulatory mechanism of cellular antiviral response.