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Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases

Black, Miles H.; Osinski, Adam; Gradowski, Marcin; Servage, Kelly A.; Pawłowski, Krzysztof LU ; Tomchick, Diana R. and Tagliabracci, Vincent S. (2019) In Science (New York, N.Y.) 364(6442). p.787-792
Abstract

Enzymes with a protein kinase fold transfer phosphate from adenosine 5'-triphosphate (ATP) to substrates in a process known as phosphorylation. Here, we show that the Legionella meta-effector SidJ adopts a protein kinase fold, yet unexpectedly catalyzes protein polyglutamylation. SidJ is activated by host-cell calmodulin to polyglutamylate the SidE family of ubiquitin (Ub) ligases. Crystal structures of the SidJ-calmodulin complex reveal a protein kinase fold that catalyzes ATP-dependent isopeptide bond formation between the amino group of free glutamate and the γ-carboxyl group of an active-site glutamate in SidE. We show that SidJ polyglutamylation of SidE, and the consequent inactivation of Ub ligase activity, is required for... (More)

Enzymes with a protein kinase fold transfer phosphate from adenosine 5'-triphosphate (ATP) to substrates in a process known as phosphorylation. Here, we show that the Legionella meta-effector SidJ adopts a protein kinase fold, yet unexpectedly catalyzes protein polyglutamylation. SidJ is activated by host-cell calmodulin to polyglutamylate the SidE family of ubiquitin (Ub) ligases. Crystal structures of the SidJ-calmodulin complex reveal a protein kinase fold that catalyzes ATP-dependent isopeptide bond formation between the amino group of free glutamate and the γ-carboxyl group of an active-site glutamate in SidE. We show that SidJ polyglutamylation of SidE, and the consequent inactivation of Ub ligase activity, is required for successful Legionella replication in a viable eukaryotic host cell.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science (New York, N.Y.)
volume
364
issue
6442
pages
6 pages
publisher
The American Association for the Advancement of Science
external identifiers
  • scopus:85066823982
ISSN
1095-9203
DOI
10.1126/science.aaw7446
language
English
LU publication?
yes
id
c857a2d9-15d5-4f6b-a000-0357c06e3981
date added to LUP
2019-07-04 09:39:32
date last changed
2019-09-17 04:58:14
@article{c857a2d9-15d5-4f6b-a000-0357c06e3981,
  abstract     = {<p>Enzymes with a protein kinase fold transfer phosphate from adenosine 5'-triphosphate (ATP) to substrates in a process known as phosphorylation. Here, we show that the Legionella meta-effector SidJ adopts a protein kinase fold, yet unexpectedly catalyzes protein polyglutamylation. SidJ is activated by host-cell calmodulin to polyglutamylate the SidE family of ubiquitin (Ub) ligases. Crystal structures of the SidJ-calmodulin complex reveal a protein kinase fold that catalyzes ATP-dependent isopeptide bond formation between the amino group of free glutamate and the γ-carboxyl group of an active-site glutamate in SidE. We show that SidJ polyglutamylation of SidE, and the consequent inactivation of Ub ligase activity, is required for successful Legionella replication in a viable eukaryotic host cell.</p>},
  author       = {Black, Miles H. and Osinski, Adam and Gradowski, Marcin and Servage, Kelly A. and Pawłowski, Krzysztof and Tomchick, Diana R. and Tagliabracci, Vincent S.},
  issn         = {1095-9203},
  language     = {eng},
  number       = {6442},
  pages        = {787--792},
  publisher    = {The American Association for the Advancement of Science},
  series       = {Science (New York, N.Y.)},
  title        = {Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases},
  url          = {http://dx.doi.org/10.1126/science.aaw7446},
  volume       = {364},
  year         = {2019},
}