4BLG

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

4BLG の概要

• エントリーDOI: 10.2210/pdb4blg/pdb
• 分子名称: LATENCY-ASSOCIATED NUCLEAR ANTIGEN, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Murid herpesvirus 4 (MURINE HERPESVIRUS 68)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32627.83

構造登録者

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. (登録日: 2013-05-02, 公開日: 2013-10-30, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)