Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin

doi:10.1110/ps.051995006

	Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin
	Chang, YG ; Song, AX ; Gao, YG ; Shi, YH; Lin, XJ ; Cao, XT ; Lin, DH ; Hu, HY
刊名	PROTEIN SCIENCE
	2006-06
卷号	15 期号:6 页码:1248-1259
关键词	ubiquitin-associated domain solution structure complex BMSC-UbP
ISSN号	0961-8368
DOI	10.1110/ps.051995006
文献子类	Article
英文摘要	Ubiquitin is an important cellular signal that targets proteins for degradation or regulates their functions. The previously identified BMSC-UbP protein derived from bone marrow stromal cells contains a ubiquitin-associated(UBA) domain at the C terminus that has been implicated in linking cellular processes and the ubiquitin system. Here, we report the solution NMR structure of the UBA domain of human BMSC-UbP protein and its complex with ubiquitin. The structure determination was facilitated by using a solubility-enhancement tag ( SET) GB1, immunoglobulin G binding domain 1 of Streptococcal protein G. The results show that BMSC-UbP UBA domain is primarily comprised of three alpha-helices with a hydrophobic patch defined by residues within the C terminus of helix-1, loop-1, and helix-3. The M-G-I motif is similar to the M/L-G-F/Y motifs conserved in most UBA domains. Chemical shift perturbation study revealed that the UBA domain binds with the conserved five-stranded beta-sheet of ubiquitin via hydrophobic interactions with the dissociation constant (KD) of similar to 17 mu M. The structural model of BMSC-UbP UBA domain complexed with ubiquitin was constructed by chemical shift mapping combined with the program HADDOCK, which is in agreement with the result from mutagenesis studies. In the complex structure, three residues (Met76, Ile78, and Leu99) of BMSC-UbP UBA form a trident anchoring the domain to the hydrophobic concave surface of ubiquitin defined by residues Leu8, Ile44, His68, and Val70. This complex structure may provide clues for BMSC-UbP functions and structural insights into the UBA domains of other ubiquitin-associated proteins that share high sequence homology with BMSC-UbP UBA domain.
WOS关键词	PROTEIN-PROTEIN INTERACTIONS ; RECEPTOR ENDOCYTOSIS ; BINDING-PROTEIN ; CUE DOMAIN ; PROTEASOME ; NMR ; DOCKING ; PATHWAY ; TSG101 ; RECOGNITION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
WOS记录号	WOS:000237927900003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273586]
专题	分析化学研究室
通讯作者	Hu, HY
作者单位	1.Shanghai Inst Biol Sci, Inst Mat Med, Shanghai 201203, Peoples R China 2.Secondary Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China 3.Shanghai Inst Biol Sci, Key Lab Proteom, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China
推荐引用方式 GB/T 7714	Chang, YG,Song, AX,Gao, YG,et al. Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin[J]. PROTEIN SCIENCE,2006,15(6):1248-1259.
APA	Chang, YG.,Song, AX.,Gao, YG.,Shi, YH.,Lin, XJ.,...&Hu, HY.(2006).Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin.PROTEIN SCIENCE,15(6),1248-1259.
MLA	Chang, YG,et al."Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin".PROTEIN SCIENCE 15.6(2006):1248-1259.