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Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ
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 Ca(2+)-binding regula...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858067/ https://www.ncbi.nlm.nih.gov/pubmed/31682223 http://dx.doi.org/10.7554/eLife.51162 |
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author | Sulpizio, Alan Minelli, Marena E Wan, Min Burrowes, Paul D Wu, Xiaochun Sanford, Ethan J Shin, Jung-Ho Williams, Byron C Goldberg, Michael L Smolka, Marcus B Mao, Yuxin |
author_facet | Sulpizio, Alan Minelli, Marena E Wan, Min Burrowes, Paul D Wu, Xiaochun Sanford, Ethan J Shin, Jung-Ho Williams, Byron C Goldberg, Michael L Smolka, Marcus B Mao, Yuxin |
author_sort | Sulpizio, Alan |
collection | PubMed |
description | 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 Ca(2+)-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. |
format | Online Article Text |
id | pubmed-6858067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-68580672019-11-18 Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ Sulpizio, Alan Minelli, Marena E Wan, Min Burrowes, Paul D Wu, Xiaochun Sanford, Ethan J Shin, Jung-Ho Williams, Byron C Goldberg, Michael L Smolka, Marcus B Mao, Yuxin eLife Structural Biology and Molecular Biophysics 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 Ca(2+)-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. eLife Sciences Publications, Ltd 2019-11-04 /pmc/articles/PMC6858067/ /pubmed/31682223 http://dx.doi.org/10.7554/eLife.51162 Text en © 2019, Sulpizio et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Sulpizio, Alan Minelli, Marena E Wan, Min Burrowes, Paul D Wu, Xiaochun Sanford, Ethan J Shin, Jung-Ho Williams, Byron C Goldberg, Michael L Smolka, Marcus B Mao, Yuxin Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title | Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title_full | Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title_fullStr | Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title_full_unstemmed | Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title_short | Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ |
title_sort | protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase sidj |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858067/ https://www.ncbi.nlm.nih.gov/pubmed/31682223 http://dx.doi.org/10.7554/eLife.51162 |
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