Two structural transitions in membrane pore formation by pneumolysin, the pore-forming toxin of Streptococcus pneumoniae

Robert J.C. Gilbert, Jose L. Jiménez, Shaoxia Chen, Ian J. Tickle, Jamie Rossjohn, Michael Parker, Peter W. Andrew, Heien R. Saibil

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160 Citations (Scopus)


The human pathogen Streptococcus pneumoniae produces soluble pneumolysin monomers that bind host cell membranes to form ring-shaped, oligomeric pores. We have determined three-dimensional structures of a helical oligomer of pneumolysin and of a membrane-bound ring form by cryo-electron microscopy. Fitting the four domains from the crystal structure of the closely related perfringolysin reveals major domain rotations during pore assembly. Oligomerization results in the expulsion of domain 3 from its original position in the monomer. However, domain 3 reassociates with the other domains in the membrane pore form. The base of domain 4 contacts the bilayer, possibly along with an extension of domain 3. These results reveal a two- stage mechanism for pore formation by the cholesterol-binding toxins.

Original languageEnglish
Pages (from-to)647-655
Number of pages9
Issue number5
Publication statusPublished - 28 May 1999
Externally publishedYes

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