Incomplete pneumolysin oligomers form membrane pores

Incomplete pneumolysin oligomers form membrane pores

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Pneumolysin is a member of the cholesterol-dependent cytolysin (CDC) family of Current Advances in Black Phosphorus‐Based Drug Delivery Systems for Cancer Therapy 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 An Exploration of Stress: Leveraging Online Data from Crowdsourcing Platforms 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.