4BLG

Crystal structure of MHV-68 Latency-associated nuclear antigen (LANA) C-terminal DNA binding domain

Summary for 4BLG

• Entry DOI: 10.2210/pdb4blg/pdb
• Descriptor: LATENCY-ASSOCIATED NUCLEAR ANTIGEN, PHOSPHATE ION (3 entities in total)
• Functional Keywords: viral protein
• Biological source: Murid herpesvirus 4 (MURINE HERPESVIRUS 68)
• Total number of polymer chains: 2
• Total formula weight: 32627.83

Authors

Correia, B.,Cerqueira, S.A.,Beauchemin, C.,Pires De Miranda, M.,Li, S.,Ponnusamy, R.,Rodrigues, L.,Schneider, T.R.,Carrondo, M.A.,Kaye, K.M.,Simas, J.P.,McVey, C.E. (deposition date: 2013-05-02, release date: 2013-10-30, Last modification date: 2023-12-20)

Primary citation

Correia, B.,Cerqueira, S.A.,Beauchemin, C.,Pires De Miranda, M.,Li, S.,Ponnusamy, R.,Rodrigues, L.,Schneider, T.R.,Carrondo, M.A.,Kaye, K.M.,Simas, J.P.,Mcvey, C.E.
Crystal Structure of the Gamma-2 Herpesvirus Lana DNA Binding Domain Identifies Charged Surface Residues which Impact Viral Latency
Plos Pathog., 9:3673-, 2013

PubMed Abstract: Latency-associated nuclear antigen (LANA) mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å 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).

PubMed: 24146618
DOI: 10.1371/JOURNAL.PPAT.1003673

Experimental method

X-RAY DIFFRACTION (2.2 Å)