The protease GtgE from Salmonella exclusively targets inactive Rab GTPases

Rudolf Wachtel, Bastian Bräuning, Sophie L. Mader, Felix Ecker, Ville R. I. Kaila, Michael Groll and Aymelt Itzen ()
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Rudolf Wachtel: Technical University of Munich
Bastian Bräuning: Technical University of Munich
Sophie L. Mader: Technical University of Munich
Felix Ecker: Technical University of Munich
Ville R. I. Kaila: Technical University of Munich
Michael Groll: Technical University of Munich
Aymelt Itzen: Technical University of Munich

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgEC45A reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02110-1

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DOI: 10.1038/s41467-017-02110-1

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