title: NMR Structure of Francisella tularensis Virulence Determinant Reveals Structural Homology to Bet v1 Allergen Proteins.
abstract: Tularemia is a potentially fatal bacterial infection caused by Francisella tularensis, and is endemic to North America and many parts of northern Europe and Asia. The outer membrane lipoprotein, Flpp3, has been identified as a virulence determinant as well as a potential subunit template for vaccine development. Here we present the first structure for the soluble domain of Flpp3 from the highly infectious Type A SCHU S4 strain, derived through high-resolution solution nuclear magnetic resonance (NMR) spectroscopy; the first structure of a lipoprotein from the genus Francisella. The Flpp3 structure demonstrates a globular protein with an electrostatically polarized surface containing an internal cavity-a putative binding site based on the structurally homologous Bet v1 protein family of allergens. NMR-based relaxation studies suggest loop regions that potentially modulate access to the internal cavity. The Flpp3 structure may add to the understanding of F. tularensis virulence and contribute to the development of effective vaccines.
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: James
authors.initials: J
authors.lastname: Zook
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Mo
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Magnetic Resonance Research Center, Arizona State University, Tempe, AZ 85287, USA; The Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ 85281, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sisco
authors.affiliation: Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA; Center for Innovations in Medicine, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
authors.forename: Felicia M
authors.initials: FM
authors.lastname: Craciunescu
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA; Center for Innovations in Medicine, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Hansen
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Bobby
authors.initials: B
authors.lastname: Baravati
authors.affiliation: Magnetic Resonance Research Center, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Cherry
authors.affiliation: Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA; Center for Innovations in Medicine, Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sykes
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wachter
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Magnetic Resonance Research Center, Arizona State University, Tempe, AZ 85287, USA; The Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ 85281, USA. Electronic address: wade.van.horn@asu.edu.
authors.forename: Wade D
authors.initials: WD
authors.lastname: Van Horn
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA; Center for Membrane Proteins in Infectious Diseases, Arizona State University, Tempe, AZ 85287, USA. Electronic address: petra.fromme@asu.edu.
authors.forename: Petra
authors.initials: P
authors.lastname: Fromme
mesh_terms: D052179:Antigens, Plant / Q000737:chemistry*; D001703:Biophysics; D015153:Blotting, Western; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D005604:Francisella tularensis / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity; D040681:Structural Homology, Protein; D037521:Virulence Factors / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D052179:Antigens, Plant; D037521:Virulence Factors; C061312:Bet v 1 allergen, Betula