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

Cell. 1999 May 28;97(5):647-55. doi: 10.1016/s0092-8674(00)80775-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins
  • Bacterial Toxins / chemistry
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure*
  • Cryoelectron Microscopy
  • Cytotoxins / chemistry
  • Hemolysin Proteins / chemistry
  • Humans
  • Models, Molecular
  • Models, Structural
  • Protein Structure, Secondary
  • Streptococcus pneumoniae / physiology*
  • Streptococcus pneumoniae / ultrastructure*
  • Streptolysins / chemistry*


  • Bacterial Proteins
  • Bacterial Toxins
  • Cytotoxins
  • Hemolysin Proteins
  • Streptolysins
  • plY protein, Streptococcus pneumoniae
  • Clostridium perfringens theta-toxin