Glutamylation of Bacterial Ubiquitin Ligases by a Legionella Pseudokinase
| Autor: | Alan Sulpizio, Marena E. Minelli, Yuxin Mao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Structural Biology and Molecular Biophysics
Crystallography X-Ray Legionella pneumophila SdeA Ligases Ubiquitin Catalytic Domain Phosphorylation 0303 health sciences biology Effector Cell biology Infectious Diseases Polyglutamic Acid Posttranslational modification Research Article Microbiology (medical) Calmodulin Legionella glutamylation Virulence Factors Ubiquitin-Protein Ligases Microbiology Article 03 medical and health sciences Bacterial Proteins Protein Domains Biochemistry and Chemical Biology Virology Humans SidJ 030304 developmental biology 030306 microbiology Ubiquitination Membrane Proteins biology.organism_classification bacterial infections and mycoses respiratory tract diseases phosphoribosyl ubiquitination HEK293 Cells biology.protein Biocatalysis bacteria Other Protein Kinases Bacteria |
| Zdroj: | Trends Microbiol eLife |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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