Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ
- Cornell University, United States
Abstract
Pseudokinases are considered to be the inactive counterparts of conventional protein kinases and comprise approximately 10% of the human and mouse kinomes. Here we report the crystal structure of the Legionella pneumophila effector protein, SidJ, in complex with the eukaryotic Ca2+-binding regulator, calmodulin (CaM). The structure reveals that SidJ contains a protein kinase-like fold domain, which retains a majority of the characteristic kinase catalytic motifs. However, SidJ fails to demonstrate kinase activity. Instead, mass spectrometry and in vitro biochemical analyses demonstrate that SidJ modifies another Legionella effector SdeA, an unconventional phosphoribosyl ubiquitin ligase, by adding glutamate molecules to a specific residue of SdeA in a CaM-dependent manner. Furthermore, we show that SidJ-mediated polyglutamylation suppresses the ADP-ribosylation activity. Our work further implies that some pseudokinases may possess ATP-dependent activities other than conventional phosphorylation.
Data availability
Diffraction data have been deposited in PDB under the accession code 6PLM
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Legionella pneumophila SidJ/ Calmodulin 2 complexProtein Data Bank, 6PLM.
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Structure of a Legionella effector with substratesProtein Data Bank, 5YIJ.
Article and author information
Author details
Michael L Goldberg
Funding
National Institute for Health Research (5R01GM116964)
- Yuxin Mao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Philip A Cole, Harvard Medical School, United States
Version history
- Received: August 17, 2019
- Accepted: November 3, 2019
- Accepted Manuscript published: November 4, 2019 (version 1)
- Version of Record published: November 15, 2019 (version 2)
Copyright
© 2019, Sulpizio et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ
eLife 8:e51162.
https://doi.org/10.7554/eLife.51162
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