title: Structural insights into the architecture of the Shigella flexneri virulence factor IcsA/VirG and motifs involved in polar distribution and secretion.
abstract: IcsA/VirG is a key virulence factor of the human pathogen Shigella flexneri, acting as both an adhesin and actin-polymerizing factor during infection. We identified a soluble expression construct of the IcsA/VirG α-domain using the ESPRIT library screening system and determined its structure to 1.9Å resolution. In addition to the previously characterized autochaperone domain, our structure reveals a new domain, which shares a common fold with the autochaperone domains of various autotransporters. We further provide insight into the previously structurally uncharacterized β-helix domain that harbors the polar targeting motif and passenger-associated transport repeat. This structure is the first of any member of the recently identified passenger-associated transport repeat-containing autotransporters. Thus, it provides new insights into the overall architecture of this class of autotransporters, the function of the identified additional autochaperone domain and the structural properties of motifs involved in polar targeting and secretion of the Shigella flexneri virulence factor IcsA/VirG.
authors.affiliation: Structural Biology of Autophagy, Helmholtz-Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leupold
authors.affiliation: Structural Biology of Autophagy, Helmholtz-Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Büsing
authors.affiliation: European Molecular Biology Laboratory Grenoble Outstation and Unit of Virus Host-Cell Interactions, University Grenoble Alpes-CNRS-EMBL, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Mas
authors.affiliation: European Molecular Biology Laboratory Grenoble Outstation and Unit of Virus Host-Cell Interactions, University Grenoble Alpes-CNRS-EMBL, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Hart
authors.affiliation: Structural Biology of Autophagy, Helmholtz-Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany. Electronic address: andrea.scrima@helmholtz-hzi.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scrima
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D015394:Molecular Structure; D000072417:Protein Domains; D021381:Protein Transport; D012763:Shigella flexneri / Q000472:pathogenicity*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D000069320:Type V Secretion Systems / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D000069320:Type V Secretion Systems; D037521:Virulence Factors; C058483:virG protein, Shigella flexneri
keywords: Autotransporter; IcsA; VirG; Virulence factor