Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases
(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
- Black, Miles H. ; Osinski, Adam ; Gradowski, Marcin ; Servage, Kelly A. ; Pawłowski, Krzysztof LU ; Tomchick, Diana R. and Tagliabracci, Vincent S.
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science (New York, N.Y.)
- volume
- 364
- issue
- 6442
- pages
- 6 pages
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- pmid:31123136
- 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
- 2022-05-11 19:50:13
@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 = {{American Association for the Advancement of Science (AAAS)}},
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}},
doi = {{10.1126/science.aaw7446}},
volume = {{364}},
year = {{2019}},
}