title: Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences.
abstract: The Legionella pneumophila Dot/Icm T4SS injects ∼ 300 protein effector proteins into host cells. Dot/Icm substrates have been proposed to contain a carboxy-terminal signal sequence that is necessary and sufficient for export, although both traits have been demonstrated for only a small fraction of these proteins. In this study, we discovered that export of the substrate SidJ is mediated by dual signal sequences that include a conventional C-terminal domain and a novel internal motif. The C-terminal signal sequence facilitates secretion of SidJ into host cells at early points of infection, whereas the internal signal sequence mediates secretion at later time points. Interestingly, only the internal signal sequence is necessary for complementation of the intracellular growth defect of a ΔsidJ mutant. Although this is the first report of a Dot/Icm substrate being secreted by an internal signal sequence, many other substrates may be exported in a similar manner. In addition, efficient translocation of SidJ is dependent on the chaperone-like type IV adaptors IcmS/IcmW. Five IcmS/IcmW binding domains that are distinct from both signal sequences were elucidated and, interestingly, only secretion mediated by the internal signal sequence requires IcmS/IcmW. Thus, Legionella employs multiple sophisticated molecular mechanisms to regulate the export of SidJ.
authors.affiliation: Department of Animal Sciences & Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Jeong
authors.forename: Molly C
authors.initials: MC
authors.lastname: Sutherland
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vogel
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D015964:Gene Expression Regulation, Bacterial; D016952:Legionella pneumophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D021381:Protein Transport
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D018832:Molecular Chaperones; D021382:Protein Sorting Signals