Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1)

Dietz, Nikolaus and Huber, Markus and Sorg, Isabel and Goepfert, Arnaud and Harms, Alexander and Schirmer, Tilman and Dehio, Christoph. (2021) Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1). Proceedings of the National Academy of Sciences, 118 (12). e2023245118.

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Official URL: https://edoc.unibas.ch/82453/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph and Sorg, Isabel and Harms, Alexander and Schirmer, Tilman and Dietz, Nikolaus and Goepfert, Arnaud
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Mar 2021 16:27
Deposited On:26 Mar 2021 16:27

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