title: Structure of the heterotrimeric complex that regulates type III secretion needle formation.
abstract: Type III secretion systems (T3SS), found in several Gram-negative pathogens, are nanomachines involved in the transport of virulence effectors directly into the cytoplasm of target cells. T3SS are essentially composed of basal membrane-embedded ring-like structures and a hollow needle formed by a single polymerized protein. Within the bacterial cytoplasm, the T3SS needle protein requires two distinct chaperones for stabilization before its secretion, without which the entire T3SS is nonfunctional. The 2.0-A x-ray crystal structure of the PscE-PscF(55-85)-PscG heterotrimeric complex from Pseudomonas aeruginosa reveals that the C terminus of the needle protein PscF is engulfed within the hydrophobic groove of the tetratricopeptide-like molecule PscG, indicating that the macromolecular scaffold necessary to stabilize the T3SS needle is totally distinct from chaperoned complexes between pilus- or flagellum-forming molecules. Disruption of specific PscG-PscF interactions leads to impairment of bacterial cytotoxicity toward macrophages, indicating that this essential heterotrimer, which possesses homologs in a wide variety of pathogens, is a unique attractive target for the development of novel antibacterials.
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel, 41 Rue Jules Horowitz, Unité Mixte de Recherche 5075, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Université Joseph Fourier, 38027 Grenoble, France.
authors.forename: Manuelle
authors.initials: M
authors.lastname: Quinaud
authors.forename: Sophie
authors.initials: S
authors.lastname: Plé
authors.forename: Viviana
authors.initials: V
authors.lastname: Job
authors.forename: Carlos
authors.initials: C
authors.lastname: Contreras-Martel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Simorre
authors.forename: Ina
authors.initials: I
authors.lastname: Attree
authors.forename: Andréa
authors.initials: A
authors.lastname: Dessen
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D015195:Drug Design; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; C506610:PscE protein, Pseudomonas aeruginosa; C506611:PscF protein, Pseudomonas aeruginosa; C506612:PscG protein, Pseudomonas aeruginosa