Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding

doi:10.1016/j.bbrc.2016.01.150

KMS > iHuman研究所

	Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding
	Jiang, Yan 1,2; Jiang, Heli 1; Zhou, Shaoyang 1; Meng, Bing 1; Liu, Zhi-Jie1,3 ; Ouyang, Songying 1
	2016-03-18
发表期刊	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (IF:2.5[JCR-2023],2.7[5-Year])
ISSN	0006-291X
卷号	471 期号:4 页码:621-627
发表状态	已发表
DOI	10.1016/j.bbrc.2016.01.150
摘要	The guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2) is identified as a member of the Dbl family of GEFs. It regulates RhoA-dependent cell signaling pathways and plays important roles in biological processes. GEF-H1 contains an N-terminal zinc finger domain, a Dbl-homologous (DH) domain followed by a Pleckstrin homology (PH) domain, and a C-terminal domain. The specific roles of its PH domain are poorly understood. Here we report the crystal structure of human GEF-H1 PH domain to 2.45 angstrom resolution. A conserved surface is formed by beta 8, beta 9, beta 10, and it may mediate protein-protein interactions. Although the folding resembles other PH domains that have defined structures, superposition of different PH domains clearly shows that the loop between beta 6/beta 7 and the loop between beta 3/beta 4 are so close that they will prevent its binding with phosphoinositide due to steric hindrance, and this has been proved by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Our studies provide a structural framework for further work on the function of GEF-H1. (C) 2016 Elsevier Inc. All rights reserved.
关键词	GEF-H1 PH domain Crystal structure Phosphoinositide
收录类别	SCI
语种	英语
资助项目	Beijing Nova Program[Z141102001814020]
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:000373242600038
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS关键词	GUANINE-NUCLEOTIDE EXCHANGE ; PLECKSTRIN HOMOLOGY DOMAINS ; RHO-GTPASES ; GEF-H1 ; PROTEIN ; KINASE ; ACTIVATION ; CLONING ; CELLS ; RAC
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1062
专题	iHuman研究所 iHuman研究所_PI研究组_刘志杰组
通讯作者	Liu, Zhi-Jie; Ouyang, Songying
作者单位	1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shanghai Tech Univ, IHuman Inst, Shanghai 201210, Peoples R China
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Jiang, Yan,Jiang, Heli,Zhou, Shaoyang,et al. Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2016,471(4):621-627.
APA	Jiang, Yan,Jiang, Heli,Zhou, Shaoyang,Meng, Bing,Liu, Zhi-Jie,&Ouyang, Songying.(2016).Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,471(4),621-627.
MLA	Jiang, Yan,et al."Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 471.4(2016):621-627.