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

Miles H. Black, Adam Osinski, Marcin Gradowski, Kelly A. Servage, Krzysztof Pawłowski, Diana R Tomchick, Vincent S Tagliabracci

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 successful Legionella replication in a viable eukaryotic host cell.

Original languageEnglish (US)
Pages (from-to)787-792
Number of pages6
JournalScience (New York, N.Y.)
Volume364
Issue number6442
DOIs
StatePublished - May 24 2019

ASJC Scopus subject areas

  • General

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