Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5

	Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5
	Zhang, Z; Zhang, TL; Wang, SS; Gong, Z; Tang, C; Chen, JY; Ding, JP
刊名	ELIFE
	2014
卷号	3 期号:1 页码:42006
通讯作者	Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jpding@sibcb.ac.cn
英文摘要	Rabex-5 and Rabaptin-5 function together to activate Rab5 and further promote early endosomal fusion in endocytosis. The Rabex-5 GEF activity is autoinhibited by the Rabex-5 CC domain (Rabex-5CC) and activated by the Rabaptin-5 C2-1 domain (Rabaptin-5C21) with yet unknown mechanism. We report here the crystal structures of Rabex-5 in complex with the dimeric Rabaptin-5C21 (Rabaptin-5C212) and in complex with Rabaptin-5C212 and Rab5, along with biophysical and biochemical analyses. We show that Rabex-5CC assumes an amphipathic a-helix which binds weakly to the substrate-binding site of the GEF domain, leading to weak autoinhibition of the GEF activity. Binding of Rabaptin-5C21 to Rabex-5 displaces Rabex-5CC to yield a largely exposed substrate-binding site, leading to release of the GEF activity. In the ternary complex the substrate-binding site of Rabex-5 is completely exposed to bind and activate Rab5. Our results reveal the molecular mechanism for the regulation of the Rabex-5 GEF activity.
学科主题	Life Sciences & Biomedicine - Other Topics
类目[WOS]	Biology
关键词[WOS]	EXCHANGE FACTOR RABEX-5 ; NUCLEOTIDE-EXCHANGE ; RAB GTPASES ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; BINDING DOMAINS ; EARLY ENDOSOMES ; FINGER DOMAIN ; EFFECTOR ; ENDOCYTOSIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000338725500002
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/297]
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	Zhang, Z,Zhang, TL,Wang, SS,et al. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5[J]. ELIFE,2014,3(1):42006.
APA	Zhang, Z.,Zhang, TL.,Wang, SS.,Gong, Z.,Tang, C.,...&Ding, JP.(2014).Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5.ELIFE,3(1),42006.
MLA	Zhang, Z,et al."Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5".ELIFE 3.1(2014):42006.