The leukocidin pore: evidence for an octamer with four LukF subunits and four LukS subunits alternating around a central axis.
The staphylococcal alpha-hemolysin (alphaHL) and leukocidin (Luk) polypeptides are members of a family of related beta-barrel pore-forming toxins. Upon binding to susceptible cells, alphaHL forms water-filled homoheptameric transmembrane pores. By contrast, Luk pores are formed by two classes of subunit, F and S, rendering a heptameric structure displeasing on symmetry grounds at least. Both the subunit stoichiometry and arrangement within the Luk pore have been contentious issues. Here we use chemical and genetic approaches to show that (1) the predominant, or perhaps the only, form of the Luk pore is an octamer; (2) the subunit stoichiometry is 1:1; and (3) the subunits are arranged in an alternating fashion about a central axis of symmetry, at least when a fused LukS-LukF construct is used. The experimental approaches we have used also open up new avenues for engineering the arrangement of the subunits of beta-barrel pore-forming toxins.
Jayasinghe
Lakmal
L
Department of Chemistry, University of Oxford, Oxford OX1 3TA, England, United Kingdom.
Bayley
Hagan
H
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006460:Hemolysin Proteins; D007956:Leukocidins; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000737:chemistry*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007956:Leukocidins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; C108483:leukocidin S-component protein, Staphylococcus; C021091:staphylococcal alpha-toxin; C074300:LukF protein, Staphylococcus aureus