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Identification of a second binding site on the TRIM25 B30.2 domain


D'Cruz, AA; Kershaw, NJ; Hayman, TJ; Linossi, EM; Chiang, JJ; Wang, MK; Dagley, LF; Kolesnik, TB; Zhang, JG; Masters, SL; Griffin, MD; Gack, MU; Murphy, JM; Nicola, NA; Babon, JJ; Nicholson, SE
2018
Biochemical Journal
Journal Article
475
2
429-440
The retinoic acid-inducible gene-I (RIG-I) receptor recognizes short 5'-di and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the tripartite motif 25 (TRIM25) B30.2 protein-interaction domain. Here we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 of RIG-I and is revealed by removal of an N-terminal alpha-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members.
Portland Press
Structural Biology; Inflammation; Systems Biology and Personalised Medicine; Cancer and Haematology; Cell Signalling and Cell Death
10.1042/BCJ20170427
29259080
Refer to article for additional funding acknowledgements
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