title: Conserved Features in the Structure, Mechanism, and Biogenesis of the Inverse Autotransporter Protein Family.
abstract: The bacterial cell surface proteins intimin and invasin are virulence factors that share a common domain structure and bind selectively to host cell receptors in the course of bacterial pathogenesis. The β-barrel domains of intimin and invasin show significant sequence and structural similarities. Conversely, a variety of proteins with sometimes limited sequence similarity have also been annotated as "intimin-like" and "invasin" in genome datasets, while other recent work on apparently unrelated virulence-associated proteins ultimately revealed similarities to intimin and invasin. Here we characterize the sequence and structural relationships across this complex protein family. Surprisingly, intimins and invasins represent a very small minority of the sequence diversity in what has been previously the "intimin/invasin protein family". Analysis of the assembly pathway for expression of the classic intimin, EaeA, and a characteristic example of the most prevalent members of the group, FdeC, revealed a dependence on the translocation and assembly module as a common feature for both these proteins. While the majority of the sequences in the grouping are most similar to FdeC, a further and widespread group is two-partner secretion systems that use the β-barrel domain as the delivery device for secretion of a variety of virulence factors. This comprehensive analysis supports the adoption of the "inverse autotransporter protein family" as the most accurate nomenclature for the family and, in turn, has important consequences for our overall understanding of the Type V secretion systems of bacterial pathogens.
authors.affiliation: Department of Microbiology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Heinz
authors.affiliation: Department of Microbiology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stubenrauch
authors.affiliation: Department of Microbiology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Rhys
authors.initials: R
authors.lastname: Grinter
authors.affiliation: Department of Biochemistry and Molecular Biology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Croft
authors.affiliation: Department of Biochemistry and Molecular Biology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: Department of Microbiology & Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Department of Microbiology, Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia trevor.lithgow@monash.edu.
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics*; D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics*; D016680:Genome, Bacterial; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D000069320:Type V Secretion Systems / Q000235:genetics; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D029968:Escherichia coli Proteins; C573009:FdeC protein, E coli; D000069320:Type V Secretion Systems; D037521:Virulence Factors; C073819:eaeA protein, E coli
keywords: BamA; TamA; beta-barrel; intimin; invasin