title: The C-terminus of IpaC is required for effector activities related to Shigella invasion of host cells.
abstract: Invasion plasmid antigen C (IpaC) is secreted by the Shigella flexneri type III secretion system (TTSS) as an essential trigger of epithelial cell invasion. At the molecular level, IpaC possesses a distinct functional organization. The IpaC C-terminal region between amino acids 319 and 345 is predicted to form a coiled-coil structure. Such alpha-helical motifs appear to be a recurring structural theme among TTSS components. Together with IpaB, this IpaC region is also required for the formation of translocon pores in target cell membranes. In contrast, mutations within the C-terminal tail of IpaC (defined by residues 345-363) have no effect on contact hemolysis (a putative measure of translocon pore formation), but they can contribute significantly to IpaC's ability to trigger S. flexneri entry into cultured cells. Here we describe the molecular dissection of the IpaC C-terminus and how changes in this region affect selected virulence-related activities. IpaC invasion function requires its immediate C-terminus and this general region may be involved in its ability to trigger actin nucleation. In contrast, IpaC could not be shown to interact directly with Cdc42, a host GTPase closely tied to Shigella invasion.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Haworth Hall Room 8047, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Terry
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Picking
authors.forename: Susan E
authors.initials: SE
authors.lastname: Birket
authors.forename: Kelly
authors.initials: K
authors.lastname: Flentie
authors.forename: Bryce M
authors.initials: BM
authors.lastname: Hoffman
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Barker
authors.forename: William D
authors.initials: WD
authors.lastname: Picking
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004405:Dysentery, Bacillary / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D012763:Shigella flexneri / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; C092342:IpaC protein, Shigella; D020764:cdc42 GTP-Binding Protein