Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases

doi:10.1002/pro.3132

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	Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases
	Chen, Yan-Na 1,5; Gu, Xin 3; Zhou, X. Edward 3; Wang, Weidong 1,5; Cheng, Dandan 1,5; Ge, Yinghua 1,5; Ye, Fei 1,5; Xu, H. Eric2,3,4 ; Lv, Zhengbing 1,5
刊名	PROTEIN SCIENCE
	2017-04
卷号	26 期号:4 页码:834-846
关键词	shark Sus TBC1D15 GAP crystal structure GTPase activity assay
ISSN号	0961-8368
DOI	10.1002/pro.3132
文献子类	Article
英文摘要	TBC1D15 belongs to the TBC (Tre-2/Bub2/Cdc16) domain family and functions as a GTPase-activating protein (GAP) for Rab GTPases. So far, the structure of TBC1D15 or the TBC1D15. Rab complex has not been determined, thus, its catalytic mechanism on Rab GTPases is still unclear. In this study, we solved the crystal structures of the Shark and Sus TBC1D15 GAP domains, to 2.8 angstrom and 2.5 angstrom resolution, respectively. Shark-TBC1D15 and Sus-TBC1D15 belong to the same subfamily of TBC domain-containing proteins, and their GAP-domain structures are highly similar. This demonstrates the evolutionary conservation of the TBC1D15 protein family. Meanwhile, the newly determined crystal structures display new variations compared to the structures of yeast Gyp1p Rab GAP domain and TBC1D1. GAP assays show that Shark and Sus GAPs both have higher catalytic activity on Rab11a.GTP than Rab7a.GTP, which differs from the previous study. We also demonstrated the importance of arginine and glutamine on the catalytic sites of Shark GAP and Sus GAP. When arginine and glutamine are changed to alanine or lysine, the activities of Shark GAP and Sus GAP are lost.
WOS关键词	SHARK LIVER ; GLUT4 TRANSLOCATION ; CRITICAL ELEMENTS ; MYOSIN VB ; PEPTIDE ; SUBSTRATE ; DISEASE ; FAMILY ; RECRUITMENT ; EXPRESSION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000398183800017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272731]
专题	药物靶标结构与功能中心
通讯作者	Xu, H. Eric; Lv, Zhengbing
作者单位	1.Zhejiang Prov Key Lab Silkworm Bioreactor & Biome, Hangzhou 310018, Zhejiang, Peoples R China; 2.Chinese Acad Sci, VARI SIMM Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China; 3.Van Andel Res Inst, Ctr Struct Biol & Drug Discovery, Lab Struct Sci, Grand Rapids, MI 49503 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 5.Zhejiang Sci Tech Univ, Coll Life Sci, Hangzhou 310018, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Chen, Yan-Na,Gu, Xin,Zhou, X. Edward,et al. Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases[J]. PROTEIN SCIENCE,2017,26(4):834-846.
APA	Chen, Yan-Na.,Gu, Xin.,Zhou, X. Edward.,Wang, Weidong.,Cheng, Dandan.,...&Lv, Zhengbing.(2017).Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases.PROTEIN SCIENCE,26(4),834-846.
MLA	Chen, Yan-Na,et al."Crystal structure of TBC1D15 GTPase-activating protein (GAP) domain and its activity on Rab GTPases".PROTEIN SCIENCE 26.4(2017):834-846.