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A covalent S‐F heterodimer of leucotoxin reveals molecular plasticity of β‐barrel pore‐forming toxins
Author(s) -
Roblin Pierre,
Guillet Valérie,
Joubert Olivier,
Keller Daniel,
Erard Monique,
Maveyraud Laurent,
Prévost Gilles,
Mourey Lionel
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21900
Subject(s) - monomer , pore forming toxin , chemistry , transmembrane protein , hemolysin , biophysics , crystallography , covalent bond , lysis , barrel (horology) , stereochemistry , biochemistry , biology , materials science , polymer , gene , toxin , microbial toxins , receptor , organic chemistry , composite material , virulence
Staphylococcal leucotoxins, leucocidins, and γ‐hemolysins are bicomponent β‐barrel pore‐forming toxins (β‐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 α‐hemolysin. These structures illustrate the start and end points in the mechanistic framework of β‐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 γ‐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 β‐PFTs, which may facilitate the transition from membrane‐bound monomers to heterodimers. Proteins 2008. © 2008 Wiley‐Liss, Inc.