The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase.
Salmonella translocate a group of type III effectors into the host cells to induce entry, promote survival and cause intestinal inflammation. Although the biochemical and cellular mechanisms of how bacterial effectors function inside host cells remain largely unknown, studies have indicated that a likely strategy is to exploit host cellular pathways through functional mimicry. We report here that SopA, a Salmonella type III effector, mimics the mammalian HECT E3 ubiquitin ligase. SopA preferentially uses the host UbcH5a, UbcH5c and UbcH7 as E2s, which are involved in inflammation. Both the wild-type SopA and the mutant SopAC753S were expressed and translocated at similar levels during the infection of HeLa cells. A Salmonella strain expressing a catalytically incompetent SopAC753S mutant had reduced Salmonella-induced polymorphonuclear leukocytes transepithelial migration. We speculate that SopA ubiquitinate bacterial/host proteins involved in Salmonella-induced intestinal inflammation.
Zhang
Ying
Y
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Higashide
Wendy M
WM
McCormick
Beth A
BA
Chen
Jue
J
Zhou
Daoguo
D
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D033862:Iron-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009504:Neutrophils / Q000382:microbiology; D017434:Protein Structure, Tertiary; D012480:Salmonella Infections / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D001426:Bacterial Proteins; D033862:Iron-Binding Proteins; C097308:UBE2D1 protein, human; C097310:UBE2D3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; C060971:SopA protein, Bacteria; D003545:Cysteine