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

Robert J.C. Gilbert, Jamie Rossjohn, Michael W. Parker, Rodney K. Tweten, Peter J. Morgan, Timothy J. Mitchell, Neil Errington, Arthur J. Rowe, Peter W. Andrew, Olwyn Byron

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68 Citations (Scopus)


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 languageEnglish
Pages (from-to)1223-1237
Number of pages15
JournalJournal of Molecular Biology
Issue number4
Publication statusPublished - 11 Dec 1998
Externally publishedYes


  • Analytical ultracentrifugation
  • Electron microscopy
  • Neutron scattering
  • Oligomerization
  • Pneumolysin

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