title: The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation.
abstract: The intracellular pathogen Legionella pneumophila can infect and replicate within macrophages of a human host. To establish infection, Legionella require the Dot/Icm secretion system to inject protein substrates directly into the host cell cytoplasm. The mechanism by which substrate proteins are engaged and translocated by the Dot/Icm system is not well understood. Here we show that two cytosolic components of the Dot/Icm secretion machinery, the proteins IcmS and IcmW, play an important role in substrate translocation. Biochemical analysis indicates that IcmS and IcmW form a stable protein complex. In Legionella, the IcmW protein is rapidly degraded in the absence of the IcmS protein. Substrate proteins translocated into mammalian host cells by the Dot/Icm system were identified using the IcmW protein as bait in a yeast two-hybrid screen. It was determined that the IcmS-IcmW complex interacts with these substrates and plays an important role in translocation of these proteins into mammalian cells. These data are consistent with the IcmS-IcmW complex being involved in the recognition and Dot/Icm-dependent translocation of substrate proteins during Legionella infection of host cells.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, Room 354b, 295 Congress Avenue, New Haven, CT 06511, USA.
authors.forename: Shira
authors.initials: S
authors.lastname: Ninio
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Zuckman-Cholon
authors.forename: Eric D
authors.initials: ED
authors.lastname: Cambronne
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D021381:Protein Transport; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins