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Publication Abstract from PubMed

Tripartite motif (TRIM) proteins primarily function as ubiquitin E3 ligases that regulate the innate immune response to infection. TRIM25 (also known as estrogen-responsive finger protein (Efp)) has been implicated in the regulation of estrogen receptor alpha signaling, and in the regulation of innate immune signaling via retinoic acid-inducible gene-I (RIG-I). RIG-I senses cytosolic viral RNA, and is subsequently ubiquitinated by TRIM25 at its N-terminal CARD domains, leading to type I interferon production. The interaction with RIG-I is dependent on the TRIM25 B30.2 domain, a protein interaction domain composed of the PRY and SPRY tandem sequence motifs. Here we present the 1.8 A crystal structure of the TRIM25 B30.2 domain, which exhibits a typical B30.2/SPRY domain fold comprising two N-terminal alpha-helices, thirteen beta-strands arranged into two beta-sheets, and loop regions of varying lengths. A comparison with other B30.2/SPRY structures and an analysis of the loop regions identified a putative binding pocket, which is likely to be involved in binding target proteins. This was supported by mutagenesis and functional analyses, which identified two key residues (Asp-488, Trp-621) in the TRIM25 B30.2 domain as being critical for binding to the RIG-I CARD domains.

Crystal Structure of the TRIM25 B30.2 (PRYSPRY) domain: A Key Component of Antiviral Signaling.,D'Cruz AA, Kershaw NJ, Chiang JJ, Wang MK, Nicola NA, Babon JJ, Gack MU, Nicholson SE Biochem J. 2013 Sep 10. PMID:24015671^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.