title: The modular structure of the inner-membrane ring component PrgK facilitates assembly of the type III secretion system basal body.
abstract: The type III secretion system (T3SS) is a large macromolecular assembly found at the surface of many pathogenic Gram-negative bacteria. Its role is to inject toxic "effector" proteins into the cells of infected organisms. The molecular details of the assembly of this large, multimembrane-spanning complex remain poorly understood. Here, we report structural, biochemical, and functional analyses of PrgK, an inner-membrane component of the prototypical Salmonella typhimurium T3SS. We have obtained the atomic structures of the two ring building globular domains and show that the C-terminal transmembrane helix is not essential for assembly and secretion. We also demonstrate that structural rearrangement of the two PrgK globular domains, driven by an interconnecting linker region, may promote oligomerization into ring structures. Finally, we used electron microscopy-guided symmetry modeling to propose a structural model for the intimately associated PrgH-PrgK ring interaction within the assembled basal body.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Julien R C
authors.initials: JRC
authors.lastname: Bergeron
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Worrall
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Soumya
authors.initials: S
authors.lastname: De
authors.affiliation: National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Sgourakis
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Cheung
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lameignere
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Okon
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wasney
authors.affiliation: Department of Biochemistry, Department of Genome Sciences, and Howard Hughes Medical Institute, University of Washington, 4000 15th Avenue NE, Seattle, WA 98195, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, 2350 Health Sciences Mall, Vancouver BC, V6T 1Z3, Canada.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: McIntosh
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. Electronic address: ncjs@mail.ubc.ca.
authors.forename: Natalie C J
authors.initials: NCJ
authors.lastname: Strynadka
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D064652:Basal Bodies / Q000737:chemistry / Q000378:metabolism*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012486:Salmonella typhimurium; D055571:Secretory Pathway; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; C079790:PrgH protein, Salmonella typhimurium; C556739:PrgK protein, Salmonella typhimurium