RRC ID 47494
著者 Omura H, Oikawa D, Nakane T, Kato M, Ishii R, Ishitani R, Tokunaga F, Nureki O.
タイトル Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide.
ジャーナル Sci Rep
Abstract 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 Å 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.
巻・号 6
ページ 34756
公開日 2016-10-10
DOI 10.1038/srep34756
PII srep34756
PMID 27721487
PMC PMC5056382
MeSH Adenosine Triphosphate / metabolism* Binding Sites Crystallography, X-Ray DEAD-box RNA Helicases / chemistry* DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism* DNA / metabolism* Humans Immunity, Innate Membrane Proteins / metabolism Models, Molecular Nucleotides, Cyclic / metabolism* Protein Binding Protein Conformation Signal Transduction
IF 3.998
引用数 15
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 CSII-EF-MCS-IRES2-Venus (RDB04384)