5gvr

Crystal structure of the DDX41 DEAD domain in an apo closed form

spinqualitylabelsall models 5gvr, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5gvr is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: LMR Related: 5gvs Gene: DDX41, ABS (HUMAN) Activity: RNA helicase, with EC number 3.6.4.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DDX41_HUMAN] Probable ATP-dependent RNA helicase. Is required during post-transcriptional gene expression. May be involved in pre-mRNA splicing. Publication Abstract from PubMed In the innate immune system, pattern recognition receptors (PRRs) specifically recognize ligands derived from bacteria or viruses, to trigger the responsible downstream pathways. DEAD box protein 41 (DDX41) is an intracellular PRR that triggers the downstream pathway involving the adapter STING, the kinase TBK1, and the transcription factor IRF3, to activate the type I interferon response. DDX41 is unique in that it recognizes two different ligands; i.e., double-stranded DNA (dsDNA) and cyclic dinucleotides (CDN), via its DEAD domain. However, the structural basis for the ligand recognition by the DDX41 DEAD domain has remained elusive. Here, we report two crystal structures of the DDX41 DEAD domain in apo forms, at 1.5 and 2.2 A resolutions. A comparison of the two crystal structures revealed the flexibility in the ATP binding site, suggesting its formation upon ATP binding. Structure-guided functional analyses in vitro and in vivo demonstrated the overlapped binding surface for dsDNA and CDN, which is distinct from the ATP-binding site. We propose that the structural rearrangement of the ATP binding site is crucial for the release of ADP, enabling the fast turnover of DDX41 for the dsDNA/CDN-induced STING activation pathway. Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide.,Omura H, Oikawa D, Nakane T, Kato M, Ishii R, Ishitani R, Tokunaga F, Nureki O Sci Rep. 2016 Oct 10;6:34756. doi: 10.1038/srep34756. PMID:27721487 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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