title: 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.
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.
authors: Division of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, 138673 Singapore, Singapore.
authors: Kelly
authors: K
authors: Hew
authors: Sue-Li
authors: SL
authors: Dahlroth
authors: Rajakannan
authors: R
authors: Venkatachalam
authors: Fariborz
authors: F
authors: Nasertorabi
authors: Bee Ting
authors: BT
authors: Lim
authors: Tobias
authors: T
authors: Cornvik
authors: Pär
authors: P
authors: Nordlund
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050835:Interferon Regulatory Factors; D014764:Viral Proteins; C413486:viral interferon regulatory factors; D004247:DNA