title: Staphylococcus aureus bicomponent gamma-hemolysins, HlgA, HlgB, and HlgC, can form mixed pores containing all components.
abstract: Staphylococcal gamma-hemolysins are bicomponent toxins forming a protein family with leucocidins and alpha-toxin. Two active toxins (AB and CB) can be formed combining one of the class-S components, HlgA or HlgC, with the class-F component HlgB. These two gamma-hemolysins form pores with marked similarities to alpha-toxin in terms of conductance, nonlinearity of the current-voltage curve, and channel stability in the open state. AB and CB pores, however, are cation-selective, whereas alpha-toxin is anion-selective. gamma-Hemolysins' pores are hetero-oligomers formed by three or four copies of each component (indicated as 3A3B and 3C3B or 4A4B and 4C4B). Point mutants located on a beta-strand of the class-S component that forms part of the protomer-protomer contact region can prevent oligomer assembly. Interestingly, these mutants inhibit growth of pores formed not only by their natural components but also by nonstandard components. This lead to the hypothesis that mixed ABC pores could also be formed. By studying the conductance of pores, assembled in the presence of all three components (in different ratios), it was observed that the magnitudes expected for mixed pores were, indeed, present. We conclude that the gamma-hemolysin/leucocidin bicomponent toxin family may form a larger than expected number of active toxins by cross-combining various S and F components.
authors.affiliation: Istituto Trentino di Cultura-Consiglio Nazionale delle Ricerche (ITC-CNR) Istituto di Biofisica, Via Sommarive 18, I-38050 Povo (Trento), Italy. mdalla@itc.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Dalla Serra
authors.forename: Manuela
authors.initials: M
authors.lastname: Coraiola
authors.forename: Gabriella
authors.initials: G
authors.lastname: Viero
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Comai
authors.forename: Cristina
authors.initials: C
authors.lastname: Potrich
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferreras
authors.forename: Lamine
authors.initials: L
authors.lastname: Baba-Moussa
authors.forename: Didier A
authors.initials: DA
authors.lastname: Colin
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Menestrina
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
authors.forename: Gilles
authors.initials: G
authors.lastname: Prévost
mesh_terms: D004912:Erythrocytes / Q000502:physiology; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000235:genetics; D006461:Hemolysis; D006801:Humans; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D016296:Mutagenesis; D010539:Permeability; D017354:Point Mutation; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000235:genetics
chemical_list: D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D008055:Lipids; D008567:Membranes, Artificial