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

Research output: Contribution to journalArticlepeer-review


  • R J Gilbert
  • J Rossjohn
  • M W Parker
  • R K Tweten
  • N Errington
  • A J Rowe
  • P W Andrew
  • O Byron

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.

Bibliographic note

Copyright 1998 Academic Press.


Original languageEnglish
Pages (from-to)1223-37
Number of pages15
JournalJournal of Molecular Biology
Issue number4
Publication statusPublished - 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