AI Article Synopsis
- Pseudokinases, like SidJ, are largely inactive versions of traditional protein kinases, making up about 10% of kinases in humans and mice.
- The structure of SidJ reveals that it has a similar shape to active kinases but lacks kinase activity; instead, it modifies another protein, SdeA, by adding glutamate.
- This modification, called polyglutamylation, can inhibit SdeA's ability to perform ADP-ribosylation, suggesting pseudokinases might have unique functions beyond typical phosphorylation.
Article 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 effector protein, SidJ, in complex with the eukaryotic Ca-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 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858067 | PMC |
| http://dx.doi.org/10.7554/eLife.51162 | DOI Listing |
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