Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone

Liu，Yongrui; Li，Yue; Bao，Hongyu; Liu，Yanhong; Chen，Liu; Huang，Hongda

2022-10-15

10.1016/j.jmb.2022.167756

JOURNAL OF MOLECULAR BIOLOGY   影响因子和分区

0022-2836

1089-8638

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.

BKRF4 Crystal structure Epstein-Barr virus tegument protein Histone chaperone

SCI

英语

第一 ; 通讯

Booz Allen Foundation[2019KSYS006];Booz Allen Foundation[2022A1515010501];Booz Allen Foundation[32171206];Booz Allen Foundation[Y01226136];

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000861022900003

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85135358348

Scopus

Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes,Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China

Liu，Yongrui,Li，Yue,Bao，Hongyu,et al. Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone[J]. JOURNAL OF MOLECULAR BIOLOGY,2022,434(19).

Liu，Yongrui,Li，Yue,Bao，Hongyu,Liu，Yanhong,Chen，Liu,&Huang，Hongda.(2022).Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone.JOURNAL OF MOLECULAR BIOLOGY,434(19).

Liu，Yongrui,et al."Epstein-Barr Virus Tegument Protein BKRF4 is a Histone Chaperone".JOURNAL OF MOLECULAR BIOLOGY 434.19(2022).