title: In Situ Molecular Architecture of the Salmonella Type III Secretion Machine.
abstract: Type III protein secretion systems have specifically evolved to deliver bacterially encoded proteins into target eukaryotic cells. The core elements of this multi-protein machine are the envelope-associated needle complex, the inner membrane export apparatus, and a large cytoplasmic sorting platform. Here, we report a high-resolution in situ structure of the Salmonella Typhimurium type III secretion machine obtained by high-throughput cryo-electron tomography and sub-tomogram averaging. Through molecular modeling and comparative analysis of machines assembled with protein-tagged components or from different deletion mutants, we determined the molecular architecture of the secretion machine in situ and localized its structural components. We also show that docking of the sorting platform results in significant conformational changes in the needle complex to provide the symmetry adaptation required for the assembly of the entire secretion machine. These studies provide major insight into the structure and assembly of a broadly distributed protein secretion machine.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Lara-Tejero
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.
authors.forename: Qingke
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: jorge.galan@yale.edu.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: jun.liu.1@uth.tmc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D021381:Protein Transport; D012486:Salmonella typhimurium / Q000648:ultrastructure*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems
keywords: Salmonella pathogenesis; bacterial pathogenesis; cryo electron tomography; molecular machines; protein secretion