title: Crystal structure of leucotoxin S component: new insight into the Staphylococcal beta-barrel pore-forming toxins.
abstract: Staphylococcal leucocidins and gamma-hemolysins (leucotoxins) are bi-component toxins that form lytic transmembrane pores. Their cytotoxic activities require the synergistic association of a class S component and a class F component, produced as water-soluble monomers that form hetero-oligomeric membrane-associated complexes. Strains that produce the Panton-Valentine leucocidin are clinically associated with cutaneous lesions and community-acquired pneumonia. In a previous study, we determined the crystal structure of the F monomer from the Panton-Valentine leucocidin. To derive information on the second component of the leucotoxins, the x-ray structure of the S protein from the Panton-Valentine leucocidin was solved to 2.0 angstrom resolution using a tetragonal crystal form that contains eight molecules in the asymmetric unit. The structure demonstrates the different conformation of the domain involved in membrane contacts and illustrates sequence and tertiary structure variabilities of the pore-forming leucotoxins. Mutagenesis studies at a key surface residue (Thr-28) further support the important role played by these microheterogeneities for the assembly of the bipartite leucotoxins.
authors.affiliation: Groupe de Biophysique Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, CNRS-IPBS, 205 route de Narbonne, 31077 Toulouse Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Guillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Roblin
authors.forename: Sandra
authors.initials: S
authors.lastname: Werner
authors.forename: Manuela
authors.initials: M
authors.lastname: Coraiola
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Menestrina
authors.forename: Henri
authors.initials: H
authors.lastname: Monteil
authors.forename: Gilles
authors.initials: G
authors.lastname: Prévost
authors.forename: Lionel
authors.initials: L
authors.lastname: Mourey
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry; D018360:Crystallography, X-Ray; D005098:Exotoxins / Q000737:chemistry*; D005434:Flow Cytometry; D006460:Hemolysin Proteins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D017550:Spectroscopy, Fourier Transform Infrared; D013210:Staphylococcus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014118:Toxins, Biological; D014965:X-Rays
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D008055:Lipids; D014118:Toxins, Biological; C018579:leukotoxin; C021091:staphylococcal alpha-toxin; D013912:Threonine