6VVC

Legionella pneumophila Lpg2603 kinase

Summary for 6VVC

• Entry DOI: 10.2210/pdb6vvc/pdb
• Descriptor: Dot/Icm T4SS effector, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: phosphorylation, kinase, transferase
• Biological source: Legionella pneumophila
• Total number of polymer chains: 1
• Total formula weight: 37903.67

Authors

Tomchick, D.R.,Tagliabracci, V.S.,Park, B.C. (deposition date: 2020-02-17, release date: 2020-04-08, Last modification date: 2024-03-06)

Primary citation

Sreelatha, A.,Nolan, C.,Park, B.C.,Pawlowski, K.,Tomchick, D.R.,Tagliabracci, V.S.
ALegionellaeffector kinase is activated by host inositol hexakisphosphate.
J.Biol.Chem., 295:6214-6224, 2020

PubMed Abstract: The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during pathogenesis.

PubMed: 32229585
DOI: 10.1074/jbc.RA120.013067

Experimental method

X-RAY DIFFRACTION (2.1 Å)