| Popis: |
The cholesterol-dependent cytolysins (CDCs) are one of the most widely distributed toxins known. The toxin gene or its product has been identified in numerous species from seven different genera of Gram-positive bacteria, including the Clostridium, Bacillus, Streptococcus, Listeria, Brevihacillus, Paenibacillus, and most recently the Arcanobacteriu. The CDCs exhibit many unique features, including an absolute dependence of their cytolytic activity on the presence of cholesterol in the membrane and also the formation of very large oligomeric pores, more than 150 A in diameter, on the membranes of cells. These toxins have been shown to be cytolytic to many eukaryotic cell types, although the bulk of the literature has focused on the hemolytic activity of these toxins. This chapter discusses the biological aspects of the toxins and recent advances in structural studies of CDC toxins. The crystal structure of PFO has proved a valuable basis for numerous structure-function studies that have revealed many details of the membrane insertion process. The structure of ILY, an atypical CDC, demonstrates that the overall protein fold first seen in PFO is almost certainly maintained in all members of the family. Key differences include different orientations of domain 4 with respect to the rest of the protein and different conformations of the undecapeptide loop, presumably in response to sequence differences in the region. Further structural studies are required to illuminate the role of cholesterol in CDC activity and the molecular detail of the CDC oligomer. |
