Crystal Structure of Leucotoxin S Component
NEW INSIGHT INTO THE STAPHYLOCOCCAL β-BARREL PORE-FORMING TOXINS*
- Valérie Guillet‡,
- Pierre Roblin‡,
- Sandra Werner§,
- Manuela Coraiola¶,
- Gianfranco Menestrina¶,
- Henri Monteil§,
- Gilles Prévost§∥ and
- Lionel Mourey‡**
- ‡Groupe de Biophysique Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, CNRS-IPBS, 205 route de Narbonne, 31077 Toulouse Cedex, France, the §Laboratoire de Physiopathologie et d'Antibiologie des Infections Bactériennes Emergentes et Nosocomiales-EA 3432, Institut de Bactériologie de la Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France, and the ¶CNR-ITC Istituto di Biofisica Sezione di Trento, Via Sommarive 18 I-38050 Povo, Italy
Abstract
Staphylococcal leucocidins and γ-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 Å 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.
- Received June 21, 2004.
- Revision received July 14, 2004.
- The American Society for Biochemistry and Molecular Biology, Inc.
