title: Contribution of the periplasmic chaperone Skp to efficient presentation of the autotransporter IcsA on the surface of Shigella flexneri.
abstract: IcsA is an outer membrane protein in the autotransporter family that is required for Shigella flexneri pathogenesis. Following its secretion through the Sec translocon, IcsA is incorporated into the outer membrane in a process that depends on YaeT, a component of an outer membrane beta-barrel insertion machinery. We investigated the role of the periplasmic chaperone Skp in IcsA maturation. Skp is required for the presentation of the mature amino terminus (alpha-domain) of IcsA on the bacterial surface and contributes to cell-to-cell spread of S. flexneri in cell culture. A mutation in skp does not prevent the insertion of the beta-barrel into the outer membrane, suggesting that the primary role of Skp is the folding of the IcsA alpha-domain. In addition, the requirement for skp can be partially bypassed by disrupting icsP, an ortholog of Escherichia coli ompT, which encodes the protease that processes IcsA between the mature amino terminus and the beta-barrel outer membrane anchor. These findings are consistent with a model in which Skp plays a critical role in the chaperoning of the alpha-domain of IcsA during transit through the periplasm.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Wagner
authors.forename: Jason E
authors.initials: JE
authors.lastname: Heindl
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Gray
authors.forename: Sumita
authors.initials: S
authors.lastname: Jain
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Goldberg
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008954:Models, Biological; D009154:Mutation; D019897:Periplasm / Q000378:metabolism*; D017510:Protein Folding; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri