title: Crystal structures of the components of the Staphylococcus aureus leukotoxin ED.
abstract: Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins that Staphylococcus aureus produces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays in S. aureus pathogenesis and the identification of its protein receptors, combined with its presence in S. aureus methicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. The two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nocadello
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: G
authors.initials: G
authors.lastname: Minasov
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shuvalova
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: I
authors.initials: I
authors.lastname: Dubrovska
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sabini
authors.affiliation: Novartis Vaccines and Diagnostics, Research Centre, Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bagnoli
authors.affiliation: Novartis Vaccines and Diagnostics, Research Centre, Siena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Center for Structural Genomics of Infectious Diseases, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: W F
authors.initials: WF
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D005098:Exotoxins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D016415:Sequence Alignment; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; C115218:LukD protein, Staphylococcus aureus; C115217:LukE protein, Staphylococcus aureus; C018579:leukotoxin
keywords: LukD; LukE; Staphylococcus aureus; leukotoxin; pore-forming toxins