Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane

doi:10.1042/BCJ20200300

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	Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane
	Ge, Liang 1,2; Wu, Bo1 ; Zhang, Youjia 1,2; Wang, Jiarong1 ; Zhao, Hongxin1 ; Wang, Junfeng 1,3
	2020-10-01
发表期刊	BIOCHEMICAL JOURNAL
ISSN	0264-6021
通讯作者	Wu, Bo(wubo@hmfl.ac.cn) ; Wang, Junfeng(junfeng@hmfl.ac.cn)
摘要	Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for Rho family GTPases that is involved in regulating a wide range of biological processes. It interacts with several tyrosine-phosphorylated cell surface receptors, including the Eph family receptors, through its SH2 domain. The interaction of Vav2 with EphA2 is crucial for EphA2-mediated tumor angiogenesis. Here we show that Vav2-SH2 domain is a lipid-binding module that can recognize PI(4,5) P2 and PI(3,4,5)P3 lipids weakly but specifically. The specific lipid-binding site in Vav2-SH2 domain was identified by NMR chemical shift perturbation experiments using the head groups of PI(4,5)P2 and PI(3,4,5)P3, both of which bind to Vav2-SH2 with millimolar binding affinities. In addition, the interaction between Vav2-SH2 and the phosphorylated juxtamembrane region (JM) of EphA2 (Y594 phosphorylated) was investigated using NMR techniques. Furthermore, by using a nickel-lipid containing peptide-based nanodiscs system, we studied the binding of Vav2-SH2 to the phosphorylated JM region of EphA2 on lipid membrane and uncovered a role of membrane environment in modulating this protein-protein recognition.
DOI	10.1042/BCJ20200300
关键词[WOS]	PHOSPHOLIPID-BILAYER NANODISCS ; STRUCTURAL BASIS ; SH2 DOMAINS ; EXCHANGE ; BINDING ; IDENTIFICATION ; AFFINITY ; PEPTIDE ; COMPLEX ; VAV-2
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[21673244] ; National Natural Science Foundation of China[U1532269] ; National Natural Science Foundation of China[U1632274] ; National Natural Science Foundation of China[U1732158] ; Ministry of Science and Technology of China[2016YFA0400901]
项目资助者	National Natural Science Foundation of China ; Ministry of Science and Technology of China
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000582387100009
出版者	PORTLAND PRESS LTD
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/104815
专题	中国科学院合肥物质科学研究院
通讯作者	Wu, Bo; Wang, Junfeng
作者单位	1.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Anhui, Peoples R China 2.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 3.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Ge, Liang,Wu, Bo,Zhang, Youjia,et al. Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane[J]. BIOCHEMICAL JOURNAL,2020,477.
APA	Ge, Liang,Wu, Bo,Zhang, Youjia,Wang, Jiarong,Zhao, Hongxin,&Wang, Junfeng.(2020).Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane.BIOCHEMICAL JOURNAL,477.
MLA	Ge, Liang,et al."Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane".BIOCHEMICAL JOURNAL 477(2020).