Self-interaction of pneumolysin, the pore-forming protein toxin of Streptococcus pneumoniae

Gilbert, R. J.C., Rossjohn, J., Parker, M. W., Tweten, R. K., Morgan, P. J., Mitchell, T. J., Errington, N., Rowe, A. J., Andrew, P. W. and Byron, O. (1998) Self-interaction of pneumolysin, the pore-forming protein toxin of Streptococcus pneumoniae. Journal of Molecular Biology, 284(4), pp. 1223-1237. (doi:10.1006/jmbi.1998.2258) (PMID:9837740)

Gilbert, R. J.C., Rossjohn, J., Parker, M. W., Tweten, R. K., Morgan, P. J., Mitchell, T. J., Errington, N., Rowe, A. J., Andrew, P. W. and Byron, O. (1998) Self-interaction of pneumolysin, the pore-forming protein toxin of Streptococcus pneumoniae. Journal of Molecular Biology, 284(4), pp. 1223-1237. (doi:10.1006/jmbi.1998.2258) (PMID:9837740)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Byron, Professor Olwyn
Authors: Gilbert, R. J.C., Rossjohn, J., Parker, M. W., Tweten, R. K., Morgan, P. J., Mitchell, T. J., Errington, N., Rowe, A. J., Andrew, P. W., and Byron, O.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Molecular Biology
Publisher:Academic Press
ISSN:0022-2836
ISSN (Online):1089-8638

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