title: Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar.
abstract: Type VI secretion systems (T6SS) are trans-envelope machines dedicated to the secretion of virulence factors into eukaryotic or prokaryotic cells, therefore required for pathogenesis and/or for competition towards neighboring bacteria. The T6SS apparatus resembles the injection device of bacteriophage T4, and is anchored to the cell envelope through a membrane complex. This membrane complex is composed of the TssL, TssM and TagL inner membrane anchored proteins and of the TssJ outer membrane lipoprotein. Here, we report the crystal structure of the enteroaggregative Escherichia coli Sci1 TssJ lipoprotein, a two four-stranded β-sheets protein that exhibits a transthyretin fold with an additional α-helical domain and a protruding loop. We showed that TssJ contacts TssM through this loop since a loop depleted mutant failed to interact with TssM in vitro or in vivo. Biophysical analysis of TssM and TssJ-TssM interaction suggest a structural model of the membrane-anchored outer shell of T6SS. Collectively, our results provide an improved understanding of T6SS assembly and encourage structure-aided drug design of novel antimicrobials targeting T6SS.
authors.affiliation: Aix-Marseille Université, Architecture et Fonction des Macromolécules Biologiques, Campus de Luminy, Marseille, France.
authors.forename: Catarina
authors.initials: C
authors.lastname: Felisberto-Rodrigues
authors.forename: Eric
authors.initials: E
authors.lastname: Durand
authors.forename: Marie-Stéphanie
authors.initials: MS
authors.lastname: Aschtgen
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blangy
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortiz-Lombardia
authors.forename: Badreddine
authors.initials: B
authors.lastname: Douzi
authors.forename: Christian
authors.initials: C
authors.lastname: Cambillau
authors.forename: Eric
authors.initials: E
authors.lastname: Cascales
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D058947:Bacterial Secretion Systems; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D055666:Lipopeptides / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; D055666:Lipopeptides; D008565:Membrane Proteins; C572322:TssJ protein, E coli; C573566:TssL protein, E coli; D037521:Virulence Factors; C043426:inner membrane protein, E coli
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