White spot syndrome virus protein ICP11: A histone-binding DNA mimic that disrupts nucleosome assembly.
White spot syndrome virus (WSSV) is a large ( approximately 300 kbp), double-stranded DNA eukaryotic virus that has caused serious disease in crustaceans worldwide. ICP11 is the most highly expressed WSSV nonstructural gene/protein, which strongly suggests its importance in WSSV infection; but until now, its function has remained obscure. We show here that ICP11 acts as a DNA mimic. In crystal, ICP11 formed a polymer of dimers with 2 rows of negatively charged spots that approximated the duplex arrangement of the phosphate groups in DNA. Functionally, ICP11 prevented DNA from binding to histone proteins H2A, H2B, H3, and H2A.x, and in hemocytes from WSSV-infected shrimp, ICP11 colocalized with histone H3 and activated-H2A.x. These observations together suggest that ICP11 might interfere with nucleosome assembly and prevent H2A.x from fulfilling its critical function of repairing DNA double strand breaks. Therefore, ICP11 possesses a functionality that is unique among the handful of presently known DNA mimic proteins.
Wang
Hao-Ching
HC
Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
Wang
Han-Ching
HC
Ko
Tzu-Ping
TP
Lee
Yu-May
YM
Leu
Jiann-Horng
JH
Ho
Chun-Han
CH
Huang
Wei-Pang
WP
Lo
Chu-Fang
CF
Wang
Andrew H-J
AH
D000818:Animals; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D006434:Hemocytes / Q000821:virology; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D033561:Penaeidae / Q000821:virology; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D046848:White spot syndrome virus 1 / Q000737:chemistry* / Q000378:metabolism
D006657:Histones; D009707:Nucleosomes; D014764:Viral Proteins; D004247:DNA