5GVR

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

Summary for 5GVR

• Entry DOI: 10.2210/pdb5gvr/pdb
• Related: 5GVS
• Descriptor: Probable ATP-dependent RNA helicase DDX41, (2S)-2-hydroxybutanedioic acid (3 entities in total)
• Functional Keywords: atpase, dead box protein, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9UJV9
• Total number of polymer chains: 1
• Total formula weight: 26308.27

Authors

Omura, H.,Oikawa, D.,Nakane, T.,Kato, M.,Ishii, R.,Goto, Y.,Suga, H.,Ishitani, R.,Tokunaga, F.,Nureki, O. (deposition date: 2016-09-06, release date: 2016-10-19, Last modification date: 2023-11-08)

Primary citation

Omura, H.,Oikawa, D.,Nakane, T.,Kato, M.,Ishii, R.,Ishitani, R.,Tokunaga, F.,Nureki, O.
Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide
Sci Rep, 6:34756-34756, 2016

PubMed 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.

PubMed: 27721487
DOI: 10.1038/srep34756

Experimental method

X-RAY DIFFRACTION (1.5 Å)