Premium
Novel export control of a L egionella Dot/Icm substrate is mediated by dual, independent signal sequences
Author(s) -
Jeong Kwang Cheol,
Sutherland Molly C.,
Vogel Joseph P.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12928
Subject(s) - signal peptide , biology , secretion , complementation , effector , microbiology and biotechnology , mutant , protein sorting signals , peptide sequence , genetics , biochemistry , gene
Summary The L egionella 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 Δ sidJ 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, L egionella employs multiple sophisticated molecular mechanisms to regulate the export of SidJ .