4HLY

The complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNA

Summary for 4HLY

• Entry DOI: 10.2210/pdb4hly/pdb
• Descriptor: K9, 5'-D(*GP*CP*GP*TP*CP*GP*AP*GP*AP*CP*GP*C)-3' (3 entities in total)
• Functional Keywords: helix-turn-helix, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Human herpesvirus 8 (HHV-8); More
• Total number of polymer chains: 4
• Total formula weight: 37995.77

Authors

Hew, K.,Venkatachalam, R. (deposition date: 2012-10-17, release date: 2013-03-13, Last modification date: 2024-03-20)

Primary citation

Hew, K.,Dahlroth, S.L.,Venkatachalam, R.,Nasertorabi, F.,Lim, B.T.,Cornvik, T.,Nordlund, P.
The crystal structure of the DNA-binding domain of vIRF-1 from the oncogenic KSHV reveals a conserved fold for DNA binding and reinforces its role as a transcription factor.
Nucleic Acids Res., 41:4295-4306, 2013

PubMed Abstract: Kaposi's sarcoma-associated herpesvirus encodes four viral homologues to cellular interferon regulatory factors (IRFs), where the most studied is vIRF-1. Even though vIRF-1 shows sequence homology to the N-terminal DNA-binding domain (DBD) of human IRFs, a specific role for this domain in vIRF-1's function has remained uncertain. To provide insights into the function of the vIRF-1 DBD, we have determined the crystal structure of it in complex with DNA and in its apo-form. Using a thermal stability shift assay (TSSA), we show that the vIRF-1 DBD binds DNA, whereas full-length vIRF-1 does not, suggesting a cis-acting regulatory mechanism in similarity to human IRFs. The complex structure of vIRF-1 DBD reveals interactions with the DNA backbone and the positioning of two arginines for specific recognition in the major grove. A superimposition with human IRF-3 reveals a similar positioning of the two specificity-determining arginines, and additional TSSAs indicate binding of vIRF-1 to an IRF-3 operator consensus sequence. The results from this study, therefore, provide support that vIRF-1 has evolved to bind DNA and plays a role in DNA binding in the context of transcriptional regulation and might act on some of the many operator sequences controlled by human IRF-3.

PubMed: 23435230
DOI: 10.1093/nar/gkt082

Experimental method

X-RAY DIFFRACTION (1.48 Å)