4B8E

PRY-SPRY domain of Trim25

Summary for 4B8E

• Entry DOI: 10.2210/pdb4b8e/pdb
• Descriptor: E3 UBIQUITIN/ISG15 LIGASE TRIM25, CHLORIDE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: ligase
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Cellular location: Cytoplasm (By similarity): Q61510
• Total number of polymer chains: 2
• Total formula weight: 45164.05

Authors

Kershaw, N.J.,D'Cruz, A.A.,Nicola, N.A.,Nicholson, S.E.,Babon, J.J. (deposition date: 2012-08-27, release date: 2013-09-04, Last modification date: 2023-12-20)

Primary citation

D'Cruz, A.A.,Kershaw, N.J.,Chiang, J.J.,Wang, M.K.,Nicola, N.A.,Babon, J.J.,Gack, M.U.,Nicholson, S.E.
Crystal Structure of the Trim25 B30.2 (Pryspry) Domain: A Key Component of Antiviral Signaling.
Biochem.J., 456:231-, 2013

PubMed Abstract: TRIM (tripartite motif) proteins primarily function as ubiquitin E3 ligases that regulate the innate immune response to infection. TRIM25 [also known as Efp (oestrogen-responsive finger protein)] has been implicated in the regulation of oestrogen receptor α signalling and in the regulation of innate immune signalling via RIG-I (retinoic acid-inducible gene-I). RIG-I senses cytosolic viral RNA and is subsequently ubiquitinated by TRIM25 at its N-terminal CARDs (caspase recruitment 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. In the present study we describe 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) and Trp(621)) in the TRIM25 B30.2 domain as being critical for binding to the RIG-I CARDs.

PubMed: 24015671
DOI: 10.1042/BJ20121425

Experimental method

X-RAY DIFFRACTION (1.779 Å)