title: Bile salt receptor complex activates a pathogenic type III secretion system.
abstract: Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Giomar
authors.initials: G
authors.lastname: Rivera-Cancel
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Kinch
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Dor
authors.initials: D
authors.lastname: Salomon
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Diana R
authors.identifier: 0000-0002-7529-4643
authors.initials: DR
authors.lastname: Tomchick
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Nick V
authors.initials: NV
authors.lastname: Grishin
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.|Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Kim
authors.identifier: 0000-0002-0678-7620
authors.initials: K
authors.lastname: Orth
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D005765:Gastrointestinal Agents / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D000069296:Type III Secretion Systems; D014736:Vibrio parahaemolyticus / Q000187:drug effects* / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D000069296:Type III Secretion Systems; D037521:Virulence Factors
keywords: Bile salt receptor; Type III Secretion system; Vibrio; biophysics; infectious disease; microbiology; pathogenesis; signaling; structural biology