title: Structural Features Reminiscent of ATP-Driven Protein Translocases Are Essential for the Function of a Type III Secretion-Associated ATPase.
abstract: Many bacterial pathogens and symbionts utilize type III secretion systems to interact with their hosts. These machines have evolved to deliver bacterial effector proteins into eukaryotic target cells to modulate a variety of cellular functions. One of the most conserved components of these systems is an ATPase, which plays an essential role in the recognition and unfolding of proteins destined for secretion by the type III pathway. Here we show that structural features reminiscent of other ATP-driven protein translocases are essential for the function of InvC, the ATPase associated with a Salmonella enterica serovar Typhimurium type III secretion system. Mutational and functional analyses showed that a two-helix-finger motif and a conserved loop located at the entrance of and within the predicted pore formed by the hexameric ATPase are essential for InvC function. These findings provide mechanistic insight into the function of this highly conserved component of type III secretion machines.
  
  
  OBJECTIVE
  Type III secretion machines are essential for the virulence or symbiotic relationships of many bacteria. These machines have evolved to deliver bacterial effector proteins into host cells to modulate cellular functions, thus facilitating bacterial colonization and replication. An essential component of these machines is a highly conserved ATPase, which is necessary for the recognition and secretion of proteins destined to be delivered by the type III secretion pathway. Using modeling and structure and function analyses, we have identified structural features of one of these ATPases from Salmonella enterica serovar Typhimurium that help to explain important aspects of its function.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Kato
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lefebre
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA jorge.galan@yale.edu.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000251:Adenosine Triphosphatases / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C088598:invC protein, Salmonella typhimurium; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases