Incomplete pneumolysin oligomers form membrane pores

  • Sonnen A
  • Plitzko J
  • Gilbert R
  • 42

    Readers

    Mendeley users who have this article in their library.
  • 36

    Citations

    Citations of this article.

Abstract

Pneumolysin is a member of the cholesterol-dependent cytolysin (CDC) family of pore-forming proteins that are produced as water-soluble monomers or dimers, bind to target membranes and oligomerize into large ring-shaped assemblies comprising approximately 40 subunits and approximately 30 nm across. This pre-pore assembly then refolds to punch a large hole in the lipid bilayer. However, in addition to forming large pores, pneumolysin and other CDCs form smaller lesions characterized by low electrical conductance. Owing to the observation of arc-like (rather than full-ring) oligomers by electron microscopy, it has been hypothesized that smaller oligomers explain smaller functional pores. To investigate whether this is the case, we performed cryo-electron tomography of pneumolysin oligomers on model lipid membranes. We then used sub-tomogram classification and averaging to determine representative membrane-bound low-resolution structures and identified pre-pores versus pores by the presence of membrane within the oligomeric curve. We found pre-pore and pore forms of both complete (ring) and incomplete (arc) oligomers and conclude that arc-shaped oligomeric assemblies of pneumolysin can form pores. As the CDCs are evolutionarily related to the membrane attack complex/perforin family of proteins, which also form variably sized pores, our findings are of relevance to that class of proteins as well.

Author-supplied keywords

  • Cryo-electron tomography
  • Pneumolysin
  • Pore formation
  • Proteolipid pore
  • Toroidal pore

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Andreas F.P. Sonnen

  • Jürgen M. Plitzko

  • Robert J.C. Gilbert

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free