title: A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of beta-barrel pore-forming toxins.
abstract: Staphylococcal leucotoxins, leucocidins, and gamma-hemolysins are bicomponent beta-barrel pore-forming toxins (beta-PFTs). Their production is associated with several clinical diseases. They have cytotoxic activity due to the synergistic action of a class S component and a class F component, which are secreted as water-soluble monomers and form hetero-oligomeric transmembrane pores, causing the lysis of susceptible cells. Structural information is currently available for the monomeric S and F proteins and the homoheptamer formed by the related alpha-hemolysin. These structures illustrate the start and end points in the mechanistic framework of beta-PFT assembly. Only limited structural data exist for the intermediate stages, including hetero-oligomeric complexes of leucotoxins. We investigated the protein-protein interactions responsible for maintaining the final bipartite molecular architecture and describe here the high-resolution crystal structure and low-resolution solution structure of a site-specific cross-linked heterodimer of gamma-hemolysin (HlgA T28C-HlgB N156C), which were solved by X-ray crystallography and small angle X-ray scattering, respectively. These structures reveal a molecular plasticity of beta-PFTs, which may facilitate the transition from membrane-bound monomers to heterodimers.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale du CNRS et de l'Université Paul Sabatier (IPBS UMR 5089), F-31077 Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roblin
authors.forename: Valérie
authors.initials: V
authors.lastname: Guillet
authors.forename: Olivier
authors.initials: O
authors.lastname: Joubert
authors.forename: Daniel
authors.initials: D
authors.lastname: Keller
authors.forename: Monique
authors.initials: M
authors.lastname: Erard
authors.forename: Laurent
authors.initials: L
authors.lastname: Maveyraud
authors.forename: Gilles
authors.initials: G
authors.lastname: Prévost
authors.forename: Lionel
authors.initials: L
authors.lastname: Mourey
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D005098:Exotoxins / Q000737:chemistry*; D011485:Protein Binding; D040141:Staphylococcaceae / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; C018579:leukotoxin