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Bacterial pore-forming toxins

We study the structure and the mechanism of action of staphylococcal two-component leucotoxins. These toxins constitute a subgroup of the β-barrel pore-forming toxin family. Their biological activity results from the synergistic action of two different proteins, S and F. S and F proteins are released as soluble monomers, which interact sequentially at the surface of target cells to form inactive oligomeric pre-pores that ultimately develop into lytic transmembrane pores.

Our goal is to structurally characterize individual proteins, including leucotoxin mutants with altered membrane-binding capability, as well oligomeric assemblies.

 

  • Laventie, B.J., Guérin, F., Mourey, L., Tawk, M.Y., Jover, E., Maveyraud, L. & Prévost, G. (2014). Residues essential for Panton-Valentine Leukocidin S component binding to its cell receptor suggest both plasticity and adaptability in its interaction surface. PLoS One9:e92094
  • Galy, R., Bergeret, F., Keller, D., Mourey, L., Prévost, G. & Maveyraud, L. (2012). Crystallization and preliminary crystallographic studies of both components of the staphylococcal LukE-LukD leukotoxin. Acta Crystallogr Sect F Struct Biol Cryst Commun 68:663-7
  • Roblin, P., Guillet, V., Joubert, O., Keller, D., Erard, M., Maveyraud, L., Prévost, G. & Mourey, L. (2008). A covalent S-F heterodimer of leucotoxin reveals molecular plasticity of beta-barrel pore-forming toxins.Proteins 71:485-96
  • Joubert, O., Voegelin, J., Guillet, V., Tranier, S., Werner, S., Colin, D. A., Dalla Serra, M., Keller, D., Monteil, H., Mourey, L. & Prévost, G. (2007). Distinction between Pore Assembly by Staphylococcal α-Toxin versus Leukotoxins. J Biomed Biotechnol 2007, 25935
  • Joubert, O., Viero, G., Keller, D., Martinez, E., Colin, D. A., Monteil, H., Mourey, L., Dalla Serra, M. & Prévost, G. Engineered covalent leucotoxin heterodimers form functional pores: insights into S-F interactions (2006). Biochem J 396:381-9
  • Prévost, G., Mourey, L., Colin, D. A., Monteil, H., Dalla Serra, M. & Menestrina, G. (2006). Alpha-helix and beta-barrel pore-forming toxins (leucocidins, alpha-, gamma- and delta-cytolysins) of Staphylococcus aureus. In: The Comprehensive Sourcebook of Bacterial Protein Toxins (Alouf, J. & Popoff, M. R., Eds), Third Edition, 588-605, Academic Press (London)
  • Guillet, V., Roblin, P., Werner, S., Coraiola, M., Menestrina, G., Monteil, H., Prévost, G. & Mourey, L. (2004). Crystal structure of leucotoxin S component: new insight into the staphylococcal beta-barrel pore-forming toxins. J Biol Chem 279:41028-37
  • Prévost, G., Mourey, L., Colin, D.A. & Menestrina, G. (2001). Staphylococcal pore-forming toxins. In: Pore-Forming Toxins (van der Goot, G., Ed.). Current Topics in Microbiology and Immunology 257:53-83
  • Pédelacq, J.D., Maveyraud, L., Prévost, G., Baba-Moussa, L., González, A., Courcelle, E., Shepard, W., Monteil, H., Samama, J.P. & Mourey, L. (1999). The structure of a Staphylococcus aureus leucocidin component (LukF-PV) reveals the fold of the water-soluble species of a family of transmembrane pore-forming toxins. Structure 7:277-87