7nx5 | pdb_00007nx5

Crystal structure of the Epstein-Barr Virus protein ZEBRA (BZLF1, Zta) bound to a methylated DNA duplex

spinqualitylabelsall models 7nx5, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nx5 is a 8 chain structure with sequence from Human gammaherpesvirus 4 and Human herpesvirus 4 strain B95-8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: 5CM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BZLF1_EBVB9 Plays a key role in the switch from latent infection to lytic cycle producing new virions. Acts as a transcription factor, inducing early lytic cycle genes, and as a origin binding protein for genome replication. BZLF1 activates the promoter of another EBV gene (BSLF2+BMLF1). Publication Abstract from PubMed In infected cells, Epstein-Barr virus (EBV) alternates between latency and lytic replication. The viral bZIP transcription factor ZEBRA (Zta, BZLF1) regulates this cycle by binding to two classes of ZEBRA response elements (ZREs): CpG-free motifs resembling the consensus AP-1 site recognized by cellular bZIP proteins and CpG-containing motifs that are selectively bound by ZEBRA upon cytosine methylation. We report structural and mutational analysis of ZEBRA bound to a CpG-methylated ZRE (meZRE) from a viral lytic promoter. ZEBRA recognizes the CpG methylation marks through a ZEBRA-specific serine and a methylcytosine-arginine-guanine triad resembling that found in canonical methyl-CpG binding proteins. ZEBRA preferentially binds the meZRE over the AP-1 site but mutating the ZEBRA-specific serine to alanine inverts this selectivity and abrogates viral replication. Our findings elucidate a DNA methylation-dependent switch in ZEBRA's transactivation function that enables ZEBRA to bind AP-1 sites and promote viral latency early during infection and subsequently, under appropriate conditions, to trigger EBV lytic replication by binding meZREs. Structural basis of DNA methylation-dependent site selectivity of the Epstein-Barr virus lytic switch protein ZEBRA/Zta/BZLF1.,Bernaudat F, Gustems M, Gunther J, Oliva MF, Buschle A, Gobel C, Pagniez P, Lupo J, Signor L, Muller CW, Morand P, Sattler M, Hammerschmidt W, Petosa C Nucleic Acids Res. 2022 Jan 11;50(1):490-511. doi: 10.1093/nar/gkab1183. PMID:34893887 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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