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Infection and Immunity, March 2002, p. 1310-1318, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1310-1318.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Retrieving Biological Activity from LukF-PV Mutants Combined with Different S Components Implies Compatibility between the Stem Domains of These Staphylococcal Bicomponent Leucotoxins

S. Werner,1 D. A. Colin,1 M. Coraiola,2 G. Menestrina,2 H. Monteil,1 and G. Prévost1*

Laboratoire de Physiopathologie et d'Antibiologie des Infections Bactériennes Emergentes et Nosocomiales, Institut de Bactériologie de la Faculté de Médecine, Université Louis Pasteur, F-67000 Strasbourg, France ,1 CNR-ITC Centro Fisica Stati Aggregati, I-38050 Povo Trento, Italy2

Received 10 July 2001/ Returned for modification 25 October 2001/ Accepted 11 December 2001

Bicomponent leucotoxins, such as Panton-Valentine leucocidin, are composed of two classes of proteins, a class S protein such as LukS-PV, which bears the cell membrane binding function, and a class F protein such as LukF-PV, which interacts to form a bipartite hexameric pore. These leucotoxins induce cell activation, linked to a Ca2+ influx, and pore formation as two consecutive and independently inhibitable events. Knowledge of the LukF-PV monomer structure has indicated that the stem domain is folded into three antiparallel ß-strands in the water-soluble form and has to refold into a transmembrane ß-hairpin during pore formation. To investigate the requirements for the cooperative assembly of the stems of the S and F components to produce biological activity, we introduced multiple deletions or single point mutations into the stem domains of LukF-PV and HlgB. While the binding of the mutated proteins was weakly dependent on these changes, Ca2+ influx and pore formation were affected differently, confirming that they are independent events. Ca2+ entry into human polymorphonuclear cells requires oligomerization and may follow the formation of a prepore. The activity of some of the LukF-PV mutants, carrying the shorter deletions, was actually improved. This demonstrated that a crucial event in the action of these toxins is the transition of the prefolded stem into the extended ß-hairpins and that this step may be facilitated by small deletions that remove some of the interactions stabilizing the folded structure.

* Corresponding author. Mailing address: Laboratoire de Physiopatholgie et d'Antibiologie des Infections Bacteriennes Emergentes et Nosocomiales--EA 3432. Institut de Bacteriologie, Universite Louis Pasteur, 3 rue Koeberle, F-67000 Strasbourg, France. Phone: 33-3-90-24-37-57. Fax: 33-3-88-25-11-13. E-mail: gilles.prevost{at}medecine.u-strasbg.fr.

Infection and Immunity, March 2002, p. 1310-1318, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1310-1318.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Meyer, F., Girardot, R., Piemont, Y., Prevost, G., Colin, D. A. (2009). Analysis of the Specificity of Panton-Valentine Leucocidin and Gamma-Hemolysin F Component Binding. Infect. Immun. 77: 266-273 [Abstract] [Full Text]  
  • Guillet, V., Roblin, P., Werner, S., Coraiola, M., Menestrina, G., Monteil, H., Prevost, G., Mourey, L. (2004). Crystal Structure of Leucotoxin S Component: NEW INSIGHT INTO THE STAPHYLOCOCCAL {beta}-BARREL PORE-FORMING TOXINS. J. Biol. Chem. 279: 41028-41037 [Abstract] [Full Text]  


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