Abstract
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.
Original language | English |
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Pages (from-to) | 1223-37 |
Number of pages | 15 |
Journal | Journal of Molecular Biology |
Volume | 284 |
Issue number | 4 |
DOIs | |
Publication status | Published - 11 Dec 1998 |
Bibliographical note
Copyright 1998 Academic Press.Keywords
- Bacterial Proteins
- Centrifugation, Density Gradient
- Macromolecular Substances
- Microscopy, Electron
- Models, Molecular
- Neutrons
- Protein Conformation
- Recombinant Proteins
- Scattering, Radiation
- Spectrophotometry
- Streptococcus pneumoniae
- Streptolysins