The dUTPase of white spot syndrome virus assembles its active sites in a noncanonical manner

doi:10.1074/jbc.M117.815266

IOCAS-IR > 实验海洋生物学重点实验室

	The dUTPase of white spot syndrome virus assembles its active sites in a noncanonical manner
	Zang, Kun 1,2,3; Li, Fuhua 1,2; Ma, Qingjun 1,2
	2018-01-19
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
卷号	293 期号:3 页码:1088-1099
文章类型	Article
摘要	dUTPases are essential enzymes for maintaining genome integrity and have recently been shown to play moonlighting roles when containing extra sequences. Interestingly, the trimeric dUTPase of white spot syndrome virus (wDUT) harbors a sequence insert at the position preceding the C-terminal catalytic motifV(pre-V insert), rarely seen in other dUTPases. However, whether this extra sequence endowswDUTwith additional properties is unknown. Herein, we present the crystal structures of wDUT in both ligand-free and ligand-bound forms. We observed that the pre-V insert in wDUT forms an unusual beta-hairpin structure in the domain-swapping region and thereby facilitates a unique orientation of the adjacent C-terminal segment, positioning the catalytic motif V onto the active site of its own subunit instead of a third subunit. Consequently, wDUT employs two-subunit active sites, unlike the widely accepted paradigm that the active site of trimeric dUTPase is contributed by all three subunits. According to results from local structural comparisons, the active-site configuration ofwDUTis similar to that of known dUTPases. However, we also found that residues in the second-shell region of the active site are reconfigured in wDUT as an adaption to its unique C-terminal orientation. We also show that deletion of the pre-V insert significantly reduces wDUT's enzymatic activity and thermal stability. We hypothesize that this rare structural arrangement confers additional functionality to wDUT. In conclusion, our study expands the structural diversity in the conserved dUTPase family and illustrates how sequence insertion and amino acid substitution drive protein evolution cooperatively.
DOI	10.1074/jbc.M117.815266
收录类别	SCI
语种	英语
WOS记录号	WOS:000422864500027
引用统计	被引频次：10[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
版本	出版稿
条目标识符	http://ir.qdio.ac.cn/handle/337002/154331
专题	实验海洋生物学重点实验室
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Nanhai Rd 7, Qingdao 266071, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266237, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
第一作者单位	中国科学院海洋研究所
推荐引用方式 GB/T 7714	Zang, Kun,Li, Fuhua,Ma, Qingjun. The dUTPase of white spot syndrome virus assembles its active sites in a noncanonical manner[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(3):1088-1099.
APA	Zang, Kun,Li, Fuhua,&Ma, Qingjun.(2018).The dUTPase of white spot syndrome virus assembles its active sites in a noncanonical manner.JOURNAL OF BIOLOGICAL CHEMISTRY,293(3),1088-1099.
MLA	Zang, Kun,et al."The dUTPase of white spot syndrome virus assembles its active sites in a noncanonical manner".JOURNAL OF BIOLOGICAL CHEMISTRY 293.3(2018):1088-1099.

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The dUTPase of white（2718KB）	期刊论文	出版稿	限制开放	CC BY-NC-SA	浏览