5EYA

TRIM25 RING domain in complex with Ubc13-Ub conjugate

Summary for 5EYA

• Entry DOI: 10.2210/pdb5eya/pdb
• Related: 4LTB
• Descriptor: Ubiquitin-conjugating enzyme E2 N, Tripartite motif-containing 25 variant, Polyubiquitin-B, ... (5 entities in total)
• Functional Keywords: complex, e3 ligase, ubiquitination, signaling protein-transferase complex, signaling protein/transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 70792.72

Authors

Pornillos, O.,Sanchez, J.G. (deposition date: 2015-11-24, release date: 2016-08-17, Last modification date: 2024-10-09)

Primary citation

Sanchez, J.G.,Chiang, J.J.,Sparrer, K.M.,Alam, S.L.,Chi, M.,Roganowicz, M.D.,Sankaran, B.,Gack, M.U.,Pornillos, O.
Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway.
Cell Rep, 16:1315-1325, 2016

PubMed 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.

PubMed: 27425606
DOI: 10.1016/j.celrep.2016.06.070

Experimental method

X-RAY DIFFRACTION (2.4 Å)