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Structural basis for selective targeting of Rac subfamily GTPases by a bacterial effector protein

Dietz, Nikolaus Balthasar and Huber, Markus and Sorg, Isabel and Goepfert, Arnaud and Harms, Alexander and Schirmer, Tilman and Dehio, Christoph. (2020) Structural basis for selective targeting of Rac subfamily GTPases by a bacterial effector protein.

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Official URL: https://edoc.unibas.ch/77694/

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Abstract

Ras-homology (Rho) family GTPases are conserved molecular switches controlling 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, molecular mechanisms of target selectivity have remained elusive. Here, we report a bacterial effector protein that targets all four Rac subfamily members of Rho family GTPases, but none of 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 motif and the Rho insert helix. Residue substitutions at the identified positions in Cdc42 facilitate modification by Bep1, while corresponding Cdc42-like substitutions in Rac1 greatly diminish modification. Our study establishes a structural paradigm for target selectivity towards 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 (Jenal) > Molecular Microbiology (Harms)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal) > Molecular Microbiology (Harms)
05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Dietz, Nikolaus and Huber, Markus and Sorg, Isabel and Goepfert, Arnaud and Harms, Alexander and Dehio, Christoph
Item Type:Working Paper
Publisher:bioRxiv
Number of Pages:25
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
Language:English
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Last Modified:08 Jul 2020 06:22
Deposited On:08 Jul 2020 06:22

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