title: Self-association of the Shigella flexneri IcsA autotransporter protein.
abstract: The IcsA autotransporter protein is a major virulence factor of the human intracellular pathogen Shigella flexneri. IcsA is distributed at the poles in the outer membrane (OM) of S. flexneri and interacts with components of the host actin-polymerization machinery to facilitate intracellular actin-based motility and subsequent cell-to-cell spreading of the bacterium. We sought to characterize the biochemical properties of IcsA in the bacterial OM. Chemical cross-linking data suggested that IcsA exists in a complex in the OM. Furthermore, reciprocal co-immunoprecipitation of differentially epitope-tagged IcsA proteins indicated that IcsA is able to self-associate. The identification of IcsA linker-insertion mutants that were negatively dominant provided genetic evidence of IcsA-IcsA interactions. From these results, we propose a model whereby IcsA self-association facilitates efficient actin-based motility.
authors.affiliation: Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: May
authors.affiliation: Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
authors.forename: Marcin
authors.initials: M
authors.lastname: Grabowicz
authors.affiliation: Discipline of Biochemistry, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Polyak
authors.affiliation: Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D011485:Protein Binding; D055503:Protein Multimerization; D012763:Shigella flexneri / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D037521:Virulence Factors; C058483:virG protein, Shigella flexneri