7VCQ

structure of viral protein BKRF4 in complex with H3.3-H4-ASF1

Summary for 7VCQ

• Entry DOI: 10.2210/pdb7vcq/pdb
• Descriptor: Histone H3.3, Histone H4, Histone chaperone ASF1B, ... (4 entities in total)
• Functional Keywords: h2a-h2b, h3-h4, histone, viral protein, nucleosome, nuclear protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 121923.51

Authors

Liu, Y.R. (deposition date: 2021-09-03, release date: 2022-08-03, Last modification date: 2023-11-29)

Primary citation

Liu, Y.,Li, Y.,Bao, H.,Liu, Y.,Chen, L.,Huang, H.
Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone.
J.Mol.Biol., 434:167756-167756, 2022

PubMed Abstract: Histone chaperones, which constitute an interaction and functional network involved in all aspects of histone metabolism, have to date been identified only in eukaryotes. The Epstein-Barr virus tegument protein BKRF4 is a histone-binding protein that engages histones H2A-H2B and H3-H4, and cellular chromatin, inhibiting the host DNA damage response. Here, we identified BKRF4 as a bona fide viral histone chaperone whose histone-binding domain (HBD) forms a co-chaperone complex with the human histone chaperone ASF1 in vitro. We determined the crystal structures of the quaternary complex of the BKRF4 HBD with human H3-H4 dimer and the histone chaperone ASF1b and the ternary complex of the BKRF4 HBD with human H2A-H2B dimer. Through structural and biochemical studies, we elucidated the molecular basis for H3-H4 and H2A-H2B recognition by BKRF4. We also revealed two conserved motifs, D/EL and DEF/Y/W, within the BKRF4 HBD, which may represent common motifs through which histone chaperones target H3-H4 and H2A-H2B, respectively. In conclusion, our results identify BKRF4 as a histone chaperone encoded by the Epstein-Barr virus, representing a typical histone chaperone found in a non-eukaryote. We envision that more histone chaperones await identification and characterization in DNA viruses and even archaea.

PubMed: 35870648
DOI: 10.1016/j.jmb.2022.167756

Experimental method

X-RAY DIFFRACTION (3 Å)