Structural highlights
Publication Abstract from PubMedLatency-associated nuclear antigen (LANA) mediates gamma2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 A resolution. The structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of Epstein-Barr virus EBNA1. A predicted DNA binding surface is present and opposite this interface is a positive electrostatic patch. Targeted DNA recognition substitutions eliminated DNA binding, while certain charged patch mutations reduced bromodomain protein, BRD4, binding. Virus containing LANA abolished for DNA binding was incapable of viable latent infection in mice. Virus with mutations at the charged patch periphery exhibited substantial deficiency in expansion of latent infection, while central region substitutions had little effect. This deficiency was independent of BRD4. These results elucidate the LANA DNA binding domain structure and reveal a unique charged region that exerts a critical role in viral latent infection, likely acting through a host cell protein(s). Crystal Structure of the Gamma-2 Herpesvirus LANA DNA Binding Domain Identifies Charged Surface Residues Which Impact Viral Latency.,Correia B, Cerqueira SA, Beauchemin C, Pires de Miranda M, Li S, Ponnusamy R, Rodrigues L, Schneider TR, Carrondo MA, Kaye KM, Simas JP, McVey CE PLoS Pathog. 2013 Oct;9(10):e1003673. doi: 10.1371/journal.ppat.1003673. Epub, 2013 Oct 17. PMID:24146618[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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