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Title: Crystal structures of the components of the Staphylococcus aureus leukotoxin ED

Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. Lastly, the two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [1]
  1. Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Center for Structural Genomics of Infectious Diseases, Dept. of Biochemistry and Molecular Genetics
  2. Novartis Vaccines and Diagnostics, Research Centre, Siena (Italy)
Publication Date:
OSTI Identifier:
1233746
Grant/Contract Number:
AC02-06CH11357; HHSN272200700058C; HHSN272201200026C
Type:
Accepted Manuscript
Journal Name:
Acta Crystallographica. Section D. Structural Biology
Additional Journal Information:
Journal Volume: 72; Journal Issue: 1; Journal ID: ISSN 2059-7983
Publisher:
IUCr
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; LukE; LukD; leukotoxin; poreforming toxins; Staphylococcus aureus