Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although most Dot/Icm-translocated effectors of Legionella pneumophila are not required for intracellular proliferation, the eukaryotic-like ankyrin effectors, AnkH and AnkJ are required for intracellular proliferation. In this report, we show that the IcmSW chaperones are essential for translocation of AnkJ but not AnkH. The 10 C-terminal residues and the ANK domains of AnkH and AnkJ are required for translocation. Our data indicate that the two ANK domains of AnkH are critical domains required for the function of the effector in intracellular replication of L. pneumophila. The ankH and ankJ mutants are severely defective in intrapulmonary proliferation in mice. Expression of AnkH and AnkJ fusions within HEK293 cells show a punctuate distribution in the cytosol but no association with endocytic vesicles, the Golgi apparatus or the endoplasmic reticulum. Interestingly, the defect in intracellular proliferation of the ankH or ankJ mutants is rescued in HEK293 cells expressing the respective protein. We conclude that AnkH and AnkJ are effectors translocated by the Dot/Icm system by distinct mechanisms and modulate distinct cytosolic processes in the host cell.
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PMID:Molecular characterization of the Dot/Icm-translocated AnkH and AnkJ eukaryotic-like effectors of Legionella pneumophila. 2002 8

The Dot/Icm-translocated Ankyrin B (AnkB) F-box effector of Legionella pneumophila is essential for intra-vacuolar proliferation and functions as a platform for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) within macrophages and ameba. Here we show that ectopically expressed AnkB in Dictyostelium discoideum is targeted to the plasma membrane where it recruits polyubiquitinated proteins and it trans-rescues the intracellular growth defect of the ankB null mutant, which has never been demonstrated for any effector in ameba. Using co-immunoprecipitation and bimolecular fluorescence complementation we show specific interaction of Skp1 of D. discoideum with the F-box domain of AnkB, which has never been demonstrated in ameba. We show that anchoring of AnkB to the cytosolic face of the LCV membrane in D. discoideum is mediated by the host farnesylation of the C-terminal eukaryotic CaaX motif of AnkB and is independent of the F-box and the two ANK domains, which has never been demonstrated in ameba. Importantly, the three host farnesylation enzymes farnesyl transferase, RCE-1, and isoprenyl cysteine carboxyl methyl transferase of D. discoideum are recruited to the LCV in a Dot/Icm-dependent manner, which has never been demonstrated in ameba. We conclude that the polyubiquitination and farnesylation enzymatic machineries of D. discoideum are recruited to the LCV in a Dot/Icm-dependent manner and the AnkB effector exploits the two evolutionarily conserved eukaryotic machineries to proliferate within ameba, similar to mammalian cells. We propose that L. pneumophila has acquired ankB through inter-kingdom horizontal gene transfer from primitive eukaryotes, which facilitated proliferation of L. pneumophila within human cells and the emergence of Legionnaires' disease.
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PMID:Molecular Characterization of Exploitation of the Polyubiquitination and Farnesylation Machineries of Dictyostelium Discoideum by the AnkB F-Box Effector of Legionella Pneumophila. 2168 15