7WLP

Epstein-Barr virus protein BKRF4 restricts nucleosome assembly to suppress host antiviral responses

7WLP の概要

• エントリーDOI: 10.2210/pdb7wlp/pdb
• 分子名称: Histone H2B type 1-O,Histone H2A type 1-D, Tegument protein BKRF4 (3 entities in total)
• 機能のキーワード: epstein-barr virus, bkrf4, histones, nucleosomes, dna double-strand break repair, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 51117.44

構造登録者

Chen, J.,Shan, S.,Zhou, Z. (登録日: 2022-01-13, 公開日: 2022-11-16, 最終更新日: 2023-11-29)

主引用文献

Chen, J.,Lu, Z.,Gong, W.,Xiao, X.,Feng, X.,Li, W.,Shan, S.,Xu, D.,Zhou, Z.
Epstein-Barr virus protein BKRF4 restricts nucleosome assembly to suppress host antiviral responses.
Proc.Natl.Acad.Sci.USA, 119:e2203782119-e2203782119, 2022

PubMed Abstract: Inhibition of host DNA damage response (DDR) is a common mechanism used by viruses to manipulate host cellular machinery and orchestrate viral life cycles. Epstein-Barr virus tegument protein BKRF4 associates with cellular chromatin to suppress host DDR signaling, but the underlying mechanism remains elusive. Here, we identify a BKRF4 histone binding domain (residues 15-102, termed BKRF4-HBD) that can accumulate at the DNA damage sites to disrupt 53BP1 foci formation. The high-resolution structure of the BKRF4-HBD in complex with a human H2A-H2B dimer shows that BKRF4-HBD interacts with the H2A-H2B dimer via the N-terminal region (NTR), the DWP motif (residues 80-86 containing D81, W84, P86), and the C-terminal region (CTR). The "triple-anchor" binding mode confers BKRF4-HBD the ability to associate with the partially unfolded nucleosomes, promoting the nucleosome disassembly. Importantly, disrupting the BKRF4-H2A-H2B interaction impairs the binding between BKRF4-HBD and nucleosome in vitro and inhibits the recruitment of BKRF4-HBD to DNA breaks in vivo. Together, our study reveals the structural basis of BKRF4 bindings to the partially unfolded nucleosome and elucidates an unconventional mechanism of host DDR signal attenuation.

PubMed: 36067323
DOI: 10.1073/pnas.2203782119

実験手法

X-RAY DIFFRACTION (2.29 Å)