Two residues at the tip of D4 (Thr and Leu) have been identified as a recognition site for cholesterol 9. The resultant PLY β-barrel pore has a diameter of ~300 Å that causes lysis of the target cell 7.ĭomain 4 (D4) is the membrane-sensing domain of CDCs and, for many CDCs, membrane-bound cholesterol appears to be the receptor 8. The monomers in the prepore undergo critical structural changes, including the unfurling of two alpha helical bundles (α-HB1 and α-HB2) in domain 3 in each monomer that are then refolded into β-hairpins (transmembrane hairpins TMH1 and TMH2) for insertion into the membrane, which is facilitated by a structural collapse towards the membrane surface 5, 6. PLY is produced as a water-soluble monomer and recognises mammalian cells via its C-terminal domain (domain 4) before assembling into circular prepores of ~30–50 monomers on the surface of cholesterol-rich membranes 3, 4. The toxin is an important candidate as a serotype-independent vaccine target against the bacterium. Pneumolysin (PLY), a major virulence factor of the bacterium 2, is a pore-forming toxin belonging to the family of cholesterol-dependent cytolysins (CDCs). The emergence of drug resistant pneumococci and the poor efficacy of pneumococcal polysaccharide vaccines have prompted the search for new vaccine and small molecule drug targets. ![]() pneumoniae accounts for a quarter of the deaths of young children in the developing world. Streptococcus pneumoniae, or pneumococcus, is the causative agent for a range of serious human diseases including pneumonia, bronchitis, bacterial meningitis, sepsis, otitis media and corneal ulcers 1, some of which lead to morbidity and mortality around the world.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |