Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin

	Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin
	Gao, YG; Yang, H; Zhao, J; Jiang, YJ; Hu, HY
刊名	STRUCTURE
	2014
卷号	22 期号:3 页码:378-386
通讯作者	Gao, YG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,yggao@sibcb.ac.cn
英文摘要	Huntington's disease (HD) is an autosomally dominant neurodegenerative disorder caused by expansion of polyglutamine (polyQ) in the huntingtin (Htt) protein. Htt yeast two-hybrid protein B (HYPB/SETD2), a histone methyltransferase, directly interacts with Htt and is involved in HD pathology. Using NMR techniques, we characterized a polyproline (polyP) stretch at the C terminus of HYPB, which directly interacts with the following WW domain and leads this domain predominantly to be in a closed conformational state. The solution structure shows that the polyP stretch extends from the back and binds to the WW core domain in a typical binding mode. This autoinhibitory structure regulates interaction between the WW domain of HYPB and the proline-rich region (PRR) of Htt, as evidenced by NMR and immunofluorescence techniques. This work provides structural and mechanistic insights into the intramolecular regulation of the WW domain in Htt-interacting partners and will be helpful for understanding the pathology of HD.
学科主题	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
关键词[WOS]	HISTONE H3 ; DISEASE PATHOGENESIS ; PROTEIN ; BINDING ; METHYLTRANSFERASE ; IDENTIFICATION ; AGGREGATION ; METHYLATION ; MECHANISMS ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000333025700004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/159]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Gao, YG,Yang, H,Zhao, J,et al. Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin[J]. STRUCTURE,2014,22(3):378-386.
APA	Gao, YG,Yang, H,Zhao, J,Jiang, YJ,&Hu, HY.(2014).Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin.STRUCTURE,22(3),378-386.
MLA	Gao, YG,et al."Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin".STRUCTURE 22.3(2014):378-386.