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TitleCryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin.
Journal, issue, pagesElife, Vol. 6, Year 2017
Publish dateMar 21, 2017
AuthorsKatharina van Pee / Alexander Neuhaus / Edoardo D'Imprima / Deryck J Mills / Werner Kühlbrandt / Özkan Yildiz /
PubMed AbstractMany pathogenic bacteria produce pore-forming toxins to attack and kill human cells. We have determined the 4.5 Å structure of the ~2.2 MDa pore complex of pneumolysin, the main virulence factor of ...Many pathogenic bacteria produce pore-forming toxins to attack and kill human cells. We have determined the 4.5 Å structure of the ~2.2 MDa pore complex of pneumolysin, the main virulence factor of , by cryoEM. The pneumolysin pore is a 400 Å ring of 42 membrane-inserted monomers. Domain 3 of the soluble toxin refolds into two ~85 Å β-hairpins that traverse the lipid bilayer and assemble into a 168-strand β-barrel. The pore complex is stabilized by salt bridges between β-hairpins of adjacent subunits and an internal α-barrel. The apolar outer barrel surface with large sidechains is immersed in the lipid bilayer, while the inner barrel surface is highly charged. Comparison of the cryoEM pore complex to the prepore structure obtained by electron cryo-tomography and the x-ray structure of the soluble form reveals the detailed mechanisms by which the toxin monomers insert into the lipid bilayer to perforate the target membrane.
External linksElife / PubMed:28323617 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.45 - 4.5 Å
Structure data

EMDB-4118, PDB-5ly6:
CryoEM structure of the membrane pore complex of Pneumolysin at 4.5A
Method: EM (single particle) / Resolution: 4.5 Å

PDB-5aoe:
Crystal structure of pneumolysin D168A mutant.
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

PDB-5aof:
Crystal structure of pneumolysin deletion mutant Delta146_147.
Method: X-RAY DIFFRACTION / Resolution: 2.45 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • streptococcus pneumoniae (bacteria)
  • streptococcus pneumoniae serotype 2 (strain d39 / nctc 7466) (bacteria)
KeywordsTOXIN / CHOLESTEROL DEPENDENT CYTOLYSIN / PORE FORMING TOXIN / Bacterial toxins / pore complex / cryoEM structure / cholesterol-dependent cytolysin / Pneumolysin / membrane pore

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