CryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Pathogenic bacteria utilize pore-forming toxins to damage host cells.
• Pneumolysin is a key virulence factor of Streptococcus pneumoniae, a common human pathogen.

Purpose of the Study:

• To determine the high-resolution structure of the pneumolysin pore complex.
• To elucidate the mechanism of pneumolysin-mediated membrane perforation.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the 4.5 Å structure of the pneumolysin pore complex.
• Comparison with structures from electron cryo-tomography (prepore) and X-ray crystallography (soluble form) was performed.

Main Results:

• The pneumolysin pore is a large ring (~2.2 MDa) composed of 42 membrane-inserted monomers.
• Monomers assemble into a 168-strand β-barrel structure, stabilized by salt bridges and an internal α-barrel.
• The pore exhibits distinct apolar outer and charged inner surfaces, facilitating lipid bilayer interaction and perforation.

Conclusions:

• The study provides detailed insights into the structural organization of the pneumolysin pore.
• The findings reveal the molecular mechanisms of toxin insertion and membrane damage by pneumolysin.