Incomplete pneumolysin oligomers form membrane pores
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....
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| Format: | Article |
| Language: | English |
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The Royal Society
2014-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140044 |
| _version_ | 1818334025981362176 |
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| author | Andreas F.-P. Sonnen Jürgen M. Plitzko Robert J. C. Gilbert |
| author_facet | Andreas F.-P. Sonnen Jürgen M. Plitzko Robert J. C. Gilbert |
| author_sort | Andreas F.-P. Sonnen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T14:00:59Z |
| format | Article |
| id | doaj.art-0033f05f19f445deb8b5e4d148e282ec |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-13T14:00:59Z |
| publishDate | 2014-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-0033f05f19f445deb8b5e4d148e282ec2022-12-21T23:42:44ZengThe Royal SocietyOpen Biology2046-24412014-01-014410.1098/rsob.140044140044Incomplete pneumolysin oligomers form membrane poresAndreas F.-P. SonnenJürgen M. PlitzkoRobert J. C. GilbertPneumolysin 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140044pneumolysinpore formationcryo-electron tomographyproteolipid poretoroidal pore |
| spellingShingle | Andreas F.-P. Sonnen Jürgen M. Plitzko Robert J. C. Gilbert Incomplete pneumolysin oligomers form membrane pores Open Biology pneumolysin pore formation cryo-electron tomography proteolipid pore toroidal pore |
| title | Incomplete pneumolysin oligomers form membrane pores |
| title_full | Incomplete pneumolysin oligomers form membrane pores |
| title_fullStr | Incomplete pneumolysin oligomers form membrane pores |
| title_full_unstemmed | Incomplete pneumolysin oligomers form membrane pores |
| title_short | Incomplete pneumolysin oligomers form membrane pores |
| title_sort | incomplete pneumolysin oligomers form membrane pores |
| topic | pneumolysin pore formation cryo-electron tomography proteolipid pore toroidal pore |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140044 |
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