Lysine11-Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila.
The fate of the polyubiquitinated protein is determined by the lysine linkages involved in the polymerization of the ubiquitin monomers, which has seven lysine residues (K(6), K(11), K(27), K(29), K(33), K(48), and K(63)). The translocated AnkB effector of the intravacuolar pathogen Legionella pneumophila is a bona fide F-box protein, which is localized to the cytosolic side of the Legionella-containing vacuole (LCV) and is essential for intravacuolar proliferation within macrophages and amoebae. The F-box domain of AnkB interacts with the host SCF1 E3 ubiquitin ligase that triggers the decoration of the LCV with K(48)-linked polyubiquitinated proteins that are targeted for proteasomal degradation. Here we report that AnkB becomes rapidly polyubiquitinated within the host cell, and this modification is independent of the F-box domain of AnkB, indicating host-mediated polyubiquitination. We show that the AnkB effector interacts specifically with the host E3 ubiquitin ligase Trim21. Mass spectrometry analyses have shown that AnkB is modified by K(11)-linked polyubiquitination, which has no effect on its stability. This work shows the first example of K(11)-linked polyubiquitination of a bacterial effector and its interaction with the host Trim21 ubiquitin ligase.
Department of Microbiology and Immunology, University of Louisville College of Medicine, Louisville, Kentucky, USA.
William M
WM
Bruckert
Department of Microbiology and Immunology, University of Louisville College of Medicine, Louisville, Kentucky, USA Center for Predictive Medicine, University of Louisville College of Medicine, Louisville, Kentucky, USA abukwaik@louisville.edu.
Yousef
Y
Abu Kwaik
D000656:Amoeba / Q000382:microbiology; D017487:Ankyrins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D044783:F-Box Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016952:Legionella pneumophila / Q000276:immunology / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000276:immunology / Q000382:microbiology; D008239:Lysine / Q000737:chemistry*; D008264:Macrophages / Q000382:microbiology; D012261:Ribonucleoproteins / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000737:chemistry; D054875:Ubiquitination; D000099207:SS-A Antigen
D017487:Ankyrins; D001426:Bacterial Proteins; D044783:F-Box Proteins; D008239:Lysine; D012261:Ribonucleoproteins; D044843:SKP Cullin F-Box Protein Ligases; D057149:Ubiquitinated Proteins; D000099207:SS-A Antigen