Crystal structure of listeriolysin O reveals molecular details of oligomerization and pore formation.

Abstract

Listeriolysin O (LLO) is an essential virulence factor of Listeria monocytogenes that causes listeriosis. Listeria monocytogenes owes its ability to live within cells to the pH- and temperature-dependent pore-forming activity of LLO, which is unique among cholesterol-dependent cytolysins. LLO enables the bacteria to cross the phagosomal membrane and is also involved in activation of cellular processes, including the modulation of gene expression or intracellular Ca(2+) oscillations. Neither the pore-forming mechanism nor the mechanisms triggering the signalling processes in the host cell are known in detail. Here, we report the crystal structure of LLO, in which we identified regions important for oligomerization and pore formation. Mutants were characterized by determining their haemolytic and Ca(2+) uptake activity. We analysed the pore formation of LLO and its variants on erythrocyte ghosts by electron microscopy and show that pore formation requires precise interface interactions during toxin oligomerization on the membrane.

• Authors: Stefan Köster, Katharina van Pee, Martina Hudel, Martin Leustik, Daniel Rhinow, Werner Kühlbrandt, Trinad Chakraborty, Özkan Yildiz
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 3690 (Apr 22 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 24751541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Biopolymers
• Heat-Shock Proteins
• Hemolysin Proteins
• hlyA protein, Listeria monocytogenes

Topics

• Amino Acid Sequence
• Bacterial Toxins (chemistry, genetics)
• Biopolymers (chemistry)
• Crystallography, X-Ray
• Heat-Shock Proteins (chemistry, genetics)
• Hemolysin Proteins (chemistry, genetics)
• Hydrogen-Ion Concentration
• Listeria (chemistry)
• Molecular Sequence Data
• Molecular Structure
• Mutation
• Sequence Homology, Amino Acid
• Temperature