气候变化领域集成服务门户(CCPortal): Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1)

CCPortal

DOI	10.1073/pnas.2023245118
	Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1)
	Dietz N.; Huber M.; Sorg I.; Goepfert A.; Harms A.; Schirmer T.; Dehio C.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Small GTPases of the Ras-homology (Rho) family are conserved molecular switches that control fundamental cellular activities in eukaryotic cells. As such, they are targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical activities and discrete target spectra; however, the molecular mechanism of target selectivity has remained largely elusive. Here we report a bacterial effector protein that selectively targets members of the Rac subfamily in the Rho family of small GTPases but none in the closely related Cdc42 or RhoA subfamilies. This exquisite target selectivity of the FIC domain AMP-transferase Bep1 from Bartonella rochalimae is based on electrostatic interactions with a subfamily-specific pair of residues in the nucleotide-binding G4 motif and the Rho insert helix. Residue substitutions at the identified positions in Cdc42 enable modification by Bep1, while corresponding Cdc42-like substitutions in Rac1 greatly diminish modification. Our study establishes a structural understanding of target selectivity toward Rac-subfamily GTPases and provides a highly selective tool for their functional analysis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	AMPylation \| structure function \| FIC domain \| RhoGTPases \| Bartonella effector protein
语种	英语
scopus关键词	adenosine phosphate; Bartonella effector protein 1; guanosine triphosphatase; protein Cdc42; Rac protein; Rac1 protein; Rho guanine nucleotide binding protein; transferase; unclassified drug; amino acid substitution; Article; Bartonella; Bartonella rochalimae; chemical modification; controlled study; nonhuman; nucleotide binding site; priority journal; protein domain; protein structure; static electricity
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180165
作者单位	Biozentrum, University of Basel, Basel, 4056, Switzerland; Ichnos Sciences Biotherapeutics SA, Epalinges, 1066, Switzerland
推荐引用方式 GB/T 7714	Dietz N.,Huber M.,Sorg I.,et al. Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1)[J],2021,118(12).
APA	Dietz N..,Huber M..,Sorg I..,Goepfert A..,Harms A..,...&Dehio C..(2021).Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1).Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Dietz N.,et al."Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1)".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).