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 (caspase activation and recruitment domains) of RIG-I and is revealed by the removal of an N-terminal α-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.
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In this issue of the Biochemical Journal, Dukic et al. report that ezrin-anchored PKA phosphorylates serine 369 and 373 on connexin 43 to enhance gap junction assembly, communication, and cell fusion. The cover image, taken from Figure 6 in the article, shows HEK293 cells transfected with mammalian expression vectors encoding siRNA-resistant Cx43 without ability to bind to ezrin and with a phosphomimicking S to D substitution in residue 369.
Identification of a second binding site on the TRIM25 B30.2 domain
Akshay A. D'Cruz, Nadia J. Kershaw, Thomas J. Hayman, Edmond M. Linossi, Jessica J. Chiang, May K. Wang, Laura F. Dagley, Tatiana B. Kolesnik, Jian-Guo Zhang, Seth L. Masters, Michael D.W. Griffin, Michaela U. Gack, James M. Murphy, Nicos A. Nicola, Jeffrey J. Babon, Sandra E. Nicholson; Identification of a second binding site on the TRIM25 B30.2 domain. Biochem J 31 January 2018; 475 (2): 429–440. doi: https://doi.org/10.1042/BCJ20170427
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