4HSC
Crystal structure of a cholesterol dependent cytolysin
Summary for 4HSC
| Entry DOI | 10.2210/pdb4hsc/pdb |
| Descriptor | Streptolysin O (2 entities in total) |
| Functional Keywords | cholesterol-dependent cytolysins, membrane insertion, membrane pore, pore-forming toxins, pore-forming toxin, toxin |
| Biological source | Streptococcus pyogenes |
| Total number of polymer chains | 1 |
| Total formula weight | 63720.29 |
| Authors | Feil, S.C.,Parker, M.W. (deposition date: 2012-10-29, release date: 2013-10-30, Last modification date: 2023-09-20) |
| Primary citation | Feil, S.C.,Ascher, D.B.,Kuiper, M.J.,Tweten, R.K.,Parker, M.W. Structural studies of Streptococcus pyogenes streptolysin O provide insights into the early steps of membrane penetration. J.Mol.Biol., 426:785-792, 2014 Cited by PubMed Abstract: Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins that exhibit a dependence on the presence of membrane cholesterol in forming large pores in cell membranes. Significant changes in the three-dimensional structure of these toxins are necessary to convert the soluble monomeric protein into a membrane pore. We have determined the crystal structure of the archetypical member of the CDC family, streptolysin O (SLO), a virulence factor from Streptococcus pyogenes. The overall fold is similar to previously reported CDC structures, although the C-terminal domain is in a different orientation with respect to the rest of the molecule. Surprisingly, a signature stretch of CDC sequence called the undecapeptide motif, a key region involved in membrane recognition, adopts a very different structure in SLO to that of the well-characterized CDC perfringolysin O (PFO), although the sequences in this region are identical. An analysis reveals that, in PFO, there are complementary interactions between the motif and the rest of domain 4 that are lost in SLO. Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and a cation-pi interaction are determining factors in the extended conformation of the motif, which in turn appears to result in a greater flexibility of the neighboring L1 loop that houses a cholesterol-sensing motif. These differences may explain the differing abilities of SLO and PFO to efficiently penetrate target cell membranes in the first step of toxin insertion into the membrane. PubMed: 24316049DOI: 10.1016/j.jmb.2013.11.020 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
Download full validation report
