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Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1

Author

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  • Jiqing Du

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
    Center for Experimental Medicine, Institute of Biochemistry and Signal Transduction, Universitätsklinikum Hamburg-Eppendorf (UKE))

  • Marie-Kristin von Wrisberg

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich, Institute for Advanced Study)

  • Burak Gulen

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
    Center for Experimental Medicine, Institute of Biochemistry and Signal Transduction, Universitätsklinikum Hamburg-Eppendorf (UKE))

  • Matthias Stahl

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
    Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet)

  • Christian Pett

    (Chemical Biology Center (KBC), Department of Chemistry, Umeå University)

  • Christian Hedberg

    (Chemical Biology Center (KBC), Department of Chemistry, Umeå University)

  • Kathrin Lang

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich, Institute for Advanced Study)

  • Sabine Schneider

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Ludwig-Maximilians-University Munich)

  • Aymelt Itzen

    (Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
    Center for Experimental Medicine, Institute of Biochemistry and Signal Transduction, Universitätsklinikum Hamburg-Eppendorf (UKE)
    Center for Structural Systems Biology (CSSB), University Medical Centre Hamburg-Eppendorf (UKE))

Abstract

Legionella pneumophila infects eukaryotic cells by forming a replicative organelle – the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.

Suggested Citation

  • Jiqing Du & Marie-Kristin von Wrisberg & Burak Gulen & Matthias Stahl & Christian Pett & Christian Hedberg & Kathrin Lang & Sabine Schneider & Aymelt Itzen, 2021. "Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20702-2
    DOI: 10.1038/s41467-020-20702-2
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    Cited by:

    1. Marietta S. Kaspers & Vivian Pogenberg & Christian Pett & Stefan Ernst & Felix Ecker & Philipp Ochtrop & Michael Groll & Christian Hedberg & Aymelt Itzen, 2023. "Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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