PDBsum entry 5gvs

Hydrolase

PDB id: 5gvs

Contents

Protein chains

216 a.a.

198 a.a.

Waters ×233

PDB id:

5gvs

Name:

Hydrolase

Title:

Crystal structure of the ddx41 dead domain in an apo open form

Structure:

Probable atp-dependent RNA helicase ddx41. Chain: a, b, c, d. Fragment: unp residues 169-399. Synonym: dead box protein 41,dead box protein abstrakt homolog. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ddx41, abs. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.211 R-free: 0.275

Authors:

H.Omura,D.Oikawa,T.Nakane,M.Kato,R.Ishii,Y.Goto,H.Suga,R.Ishitani, F.Tokunaga,O.Nureki

Key ref:

H.Omura et al. (2016). Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide. Sci Rep, 6, 34756. PubMed id: 27721487

Date:

06-Sep-16 Release date: 19-Oct-16

Protein chains

Q9UJV9  (DDX41_HUMAN) -  Probable ATP-dependent RNA helicase DDX41 from Homo sapiens

Seq: 622 a.a.

Struc: 216 a.a.

Protein chains

Q9UJV9  (DDX41_HUMAN) -  Probable ATP-dependent RNA helicase DDX41 from Homo sapiens

Seq: 622 a.a.

Struc: 198 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Sci Rep 6:34756 (2016)

PubMed id: 27721487

Structural and Functional Analysis of DDX41: a bispecific immune receptor for DNA and cyclic dinucleotide.

H.Omura, D.Oikawa, T.Nakane, M.Kato, R.Ishii, R.Ishitani, F.Tokunaga, O.Nureki.

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.