Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25

doi:10.1016/j.bpj.2017.04.022

	Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25
	Yang, Yuanyuan 1,2; Shi, Li 1,2; Ding, Yiluan 2; Shi, Yanhong2 ; Hu, Hong-Yu 3; Wen, Yi 2; Zhang, Naixia1,2
刊名	BIOPHYSICAL JOURNAL
	2017-05-23
卷号	112 期号:10 页码:2099-2108
ISSN号	0006-3495
DOI	10.1016/j.bpj.2017.04.022
文献子类	Article
英文摘要	Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well. To test our hypothesis and elucidate the underlying molecular mechanism, we investigated the structure and function of the Usp25 N-terminal UBR. The solution structure of Usp25(1-146) is obtained, and the key residues responsible for recognition of ubiquitin and SUMO2 are identified. Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif. We also find that SUMO2 can competitively block the interaction between the Usp25 UBR and its ubiquitin substrates. Based on our findings, we have proposed a working model to depict the regulatory role of the Usp25 UBR in the functional display of the enzyme.
资助项目	Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120164002] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CASIMM0120163013] ; National Natural Science Foundation of China[21272246] ; National Natural Science Foundation of China[31300608] ; National Key Basic Research Program of China[2013CB910900]
WOS关键词	MOLECULAR-STRUCTURE DETERMINATION ; DEUBIQUITINATING ENZYMES ; PROTEASE USP25 ; EMERGING ROLES ; MODIFIER SUMO ; XPLOR-NIH ; CANCER ; NMR ; DOMAINS ; RECOGNITION
WOS研究方向	Biophysics
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000402119300010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272655]
专题	分析化学研究室
通讯作者	Wen, Yi; Zhang, Naixia
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Yang, Yuanyuan,Shi, Li,Ding, Yiluan,et al. Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25[J]. BIOPHYSICAL JOURNAL,2017,112(10):2099-2108.
APA	Yang, Yuanyuan.,Shi, Li.,Ding, Yiluan.,Shi, Yanhong.,Hu, Hong-Yu.,...&Zhang, Naixia.(2017).Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25.BIOPHYSICAL JOURNAL,112(10),2099-2108.
MLA	Yang, Yuanyuan,et al."Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25".BIOPHYSICAL JOURNAL 112.10(2017):2099-2108.