Crystal Structure of the TRIM25 B30.2 (PRYSPRY) domain: A Key Component of Antiviral Signaling

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 α 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 Å crystal structure of the TRIM25 B30.2 domain, which exhibits a typical B30.2/SPRY domain fold comprising two N-terminal α-helices, thirteen β-strands arranged into two β-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.

Source: BJ Signal - September 10, 2013 Category: Biochemistry Authors: A Antonio D'Cruz, N J Kershaw, J J Chiang, M K Wang, N A Nicola, J J Babon, M U Gack, S E Nicholson Tags: BJ Biomolecules Source Type: research