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

R J Gilbert, J Rossjohn, M W Parker, R K Tweten, P J Morgan, T J Mitchell, N Errington, A J Rowe, P W Andrew, O Byron

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

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 languageEnglish
Pages (from-to)1223-37
Number of pages15
JournalJournal of Molecular Biology
Volume284
Issue number4
DOIs
Publication statusPublished - 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

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