title: Structure of a type IV secretion system.
abstract: Bacterial type IV secretion systems translocate virulence factors into eukaryotic cells, distribute genetic material between bacteria and have shown potential as a tool for the genetic modification of human cells. Given the complex choreography of the substrate through the secretion apparatus, the molecular mechanism of the type IV secretion system has proved difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy to reconstruct the type IV secretion system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form an approximately 3 megadalton nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of 12 VirB4 ATPase subunits organized as side-by-side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems.
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Harry H
authors.initials: HH
authors.lastname: Low
authors.affiliation: Institut Pasteur, G5 Biologie structurale de la sécrétion bactérienne and UMR 3528-CNRS, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gubellini
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Angel
authors.initials: A
authors.lastname: Rivera-Calzada
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Braun
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Connery
authors.affiliation: Institut Pasteur, G5 Biologie structurale de la sécrétion bactérienne and UMR 3528-CNRS, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Dujeancourt
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Redzej
authors.affiliation: Institut Pasteur, G5 Biologie structurale de la sécrétion bactérienne and UMR 3528-CNRS, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Fronzes
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Orlova
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London, WC1E 7HX, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Waksman
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D058947:Bacterial Secretion Systems / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000166:cytology / Q000235:genetics / Q000648:ultrastructure*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; D046912:Multiprotein Complexes; D000251:Adenosine Triphosphatases