3JRV

Structure of poxvirus K7 protein in complex with RNA helicase DDX3

Summary for 3JRV

• Entry DOI: 10.2210/pdb3jrv/pdb
• Descriptor: Protein K7, ATP-dependent RNA helicase DDX3X (3 entities in total)
• Functional Keywords: poxvirus protein k7, dead-box rna helicase ddx3, viral immune evasion, innate immunity, viral protein-protein binding complex, viral protein/protein binding
• Biological source: Vaccinia virus WR (VACV); More
• Cellular location: Nucleus speckle: O00571
• Total number of polymer chains: 5
• Total formula weight: 41827.71

Authors

Oda, S.,Khan, R.A. (deposition date: 2009-09-09, release date: 2009-11-10, Last modification date: 2024-11-20)

Primary citation

Oda, S.,Schroder, M.,Khan, A.R.
Structural basis for targeting of human RNA helicase DDX3 by poxvirus protein K7
Structure, 17:1528-1537, 2009

PubMed Abstract: Poxviruses are DNA viruses that express numerous proteins to subvert the host immune response. Vaccinia virus protein K7 adopts a Bcl-2 fold and displays structural and functional similarities to Toll-like receptor antagonist A52. Both proteins interact with IRAK2 and TRAF6 and suppress TLR-dependent NF-kappaB activation. However, unlike A52, K7 also forms a complex with RNA helicase DDX3 and antagonizes interferon-beta promoter induction. We have narrowed the K7 binding site to an N-terminal peptide motif of DDX3 ahead of its core RNA-helicase domains. The crystal structure of full-length K7 in complex with the DDX3 peptide reveals a thumblike projection of tandem phenalyalanine residues of DDX3 into a deep hydrophobic cleft. Mutagenesis of these phenylalanines abolishes the effects of DDX3 on interferon-beta promoter induction. The structure of K7-DDX3 reveals a novel binding mode by a viral Bcl-2 protein that antagonizes a key pathway in innate immunity.

PubMed: 19913487
DOI: 10.1016/j.str.2009.09.005

Experimental method

X-RAY DIFFRACTION (1.6 Å)