Self-interaction of pneumolysin, the pore-forming protein toxin of Streptococcus pneumoniae
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
The pathogenically important cholesterol-binding pore-forming bacterial "thiol-activated" toxins (TATs) are commonly believed to be monomeric in solution and to undergo a transition on membrane binding mediated by cholesterol to an oligomeric pore. We present evidence, gained through the application of a number of biochemical and biophysical techniques with associated modelling, that the TAT from Streptococcus pneumoniae, pneumolysin, is in fact able to self-associate in solution to form the same oligomeric structures. The weak interaction leading to solution oligomerization is manifested at low concentrations in a dimeric toxin form. The inhibition of toxin self-interaction by derivatization of the single cysteine residue in pneumolysin with the thiol-active agent dithio (bis)nitrobenzoic acid indicates that self-interaction is mediated by the fourth domain of the protein, which has a fold similar to other proteins known to self-associate. This interaction is thought to have implications for the understanding of mechanisms of pore formation and complement activation by pneumolysin.
|Number of pages||15|
|Journal||Journal of Molecular Biology|
|Publication status||Published - 11 Dec 1998|
- Bacterial Proteins, Centrifugation, Density Gradient, Macromolecular Substances, Microscopy, Electron, Models, Molecular, Neutrons, Protein Conformation, Recombinant Proteins, Scattering, Radiation, Spectrophotometry, Streptococcus pneumoniae, Streptolysins