RT Journal Article
SR Electronic
T1 Protein polyglutamylation catalyzed by the bacterial Calmodulin-dependent pseudokinase SidJ
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 738567
DO 10.1101/738567
A1 Alan Sulpizio
A1 Marena E. Minelli
A1 Min Wan
A1 Paul D. Burrowes
A1 Xiaochun Wu
A1 Ethan Sanford
A1 Jung-Ho Shin
A1 Byron Williams
A1 Michael Goldberg
A1 Marcus B. Smolka
A1 Yuxin Mao
YR 2019
UL http://biorxiv.org/content/early/2019/08/20/738567.abstract
AB 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 analysis 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.