Structural and functional studies of USP20 ZnF-UBP domain by NMR

doi:10.1002/pro.3675

	Structural and functional studies of USP20 ZnF-UBP domain by NMR
	Yang, Yuanyuan 1,2; Ding, Yiluan 1; Zhou, Chen 1; Wen, Yi 3; Zhang, Naixia 1,2
刊名	PROTEIN SCIENCE
	2019-09-01
卷号	28 期号:9 页码:1606-1619
关键词	deubiquitinase NMR solution structure USP20 ZnF-UBP domain
ISSN号	0961-8368
DOI	10.1002/pro.3675
通讯作者	Zhang, Naixia(nxzhang@simm.ac.cn)
英文摘要	Deubiquitinase USP20/VDU2 has been demonstrated to play important roles in multiple cellular processes by controlling the life span of substrate proteins including hypoxia-inducible factor HIF1 alpha, and so forth. USP20 contains four distinct structural domains including the N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP), the catalytic domain (USP domain), and two tandem DUSP domains, and none of the structures for these four domains has been solved. Meanwhile, except for the ZnF-UBP domain, the biological functions for USP20's catalytic domain and tandem DUSP domains have been at least partially clarified. Here in this study, we determined the solution structure of USP20 ZnF-UBP domain and investigated its binding properties with mono-ubiquitin and poly-ubiquitin (K48-linked di-ubiquitin) by using NMR and molecular modeling techniques. USP20's ZnF-UBP domain forms a spherically shaped fold consisting of a central beta-sheet with either one alpha-helix or two alpha-helices packed on each side of the sheet. However, although having formed a canonical core structure essential for ubiquitin recognition, USP20 ZnF-UBP presents weak ubiquitin binding capacity. The structural basis for understanding USP20 ZnF-UBP's ubiquitin binding capacity was revealed by NMR data-driven docking. Although the electrostatic interactions between D264 of USP5 (E87 in USP20 ZnF-UBP) and R74 of ubiquitin are kept, the loss of the extensive interactions formed between ubiquitin's di-glycine motif and the conserved and non-conserved residues of USP20 ZnF-UBP domain (W41, E55, and Y84) causes a significant decrease in its binding affinity to ubiquitin. Our findings indicate that USP20 ZnF-UBP domain might have a physiological role unrelated to its ubiquitin binding capacity.
资助项目	National Natural Science Foundation of China[21778061] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002]
WOS关键词	XPLOR-NIH ; UBIQUITIN ; ENZYMES ; INSIGHTS ; DEUBIQUITINATION ; PHOSPHORYLATION ; SPECIFICITY ; RECOGNIZES ; ACTIVATION ; MECHANISMS
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000481129000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288934]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Naixia
作者单位	1.Chinese Acad Sci, Dept Analyt Chem, Shanghai Inst Materia Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Oxford Instruments Technol Shanghai Co Ltd, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Yang, Yuanyuan,Ding, Yiluan,Zhou, Chen,et al. Structural and functional studies of USP20 ZnF-UBP domain by NMR[J]. PROTEIN SCIENCE,2019,28(9):1606-1619.
APA	Yang, Yuanyuan,Ding, Yiluan,Zhou, Chen,Wen, Yi,&Zhang, Naixia.(2019).Structural and functional studies of USP20 ZnF-UBP domain by NMR.PROTEIN SCIENCE,28(9),1606-1619.
MLA	Yang, Yuanyuan,et al."Structural and functional studies of USP20 ZnF-UBP domain by NMR".PROTEIN SCIENCE 28.9(2019):1606-1619.