Toxicity of an α-Pore-forming toxin depends on the assembly mechanism on the target membrane as revealed by single molecule imaging
α-Pore-forming toxins (α-PFTs) are ubiquitous defense tools that kill cells by opening pores in the target cell membrane. Despite their relevance in host/pathogen interactions, very little is known about the pore stoichiometry and assembly pathway leading to membrane permeabilization. Equinatoxin II...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2015
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| In: |
The journal of biological chemistry
Year: 2014, Volume: 290, Issue: 8, Pages: 4856-4865 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.600676 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M114.600676 Verlag, lizenzpflichtig, Volltext: http://www.jbc.org/content/290/8/4856 
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| Author Notes: | Yamunadevi Subburaj, Uris Ros, Eduard Hermann, Rudi Tong, and Ana J. García-Sáez |
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| 520 | |a α-Pore-forming toxins (α-PFTs) are ubiquitous defense tools that kill cells by opening pores in the target cell membrane. Despite their relevance in host/pathogen interactions, very little is known about the pore stoichiometry and assembly pathway leading to membrane permeabilization. Equinatoxin II (EqtII) is a model α-PFT from sea anemone that oligomerizes and forms pores in sphingomyelin-containing membranes. Here, we determined the spatiotemporal organization of EqtII in living cells by single molecule imaging. Surprisingly, we found that on the cell surface EqtII did not organize into a unique oligomeric form. Instead, it existed as a mixture of oligomeric species mostly including monomers, dimers, tetramers, and hexamers. Mathematical modeling based on our data supported a new model in which toxin clustering happened in seconds and proceeded via condensation of EqtII dimer units formed upon monomer association. Furthermore, altering the pathway of EqtII assembly strongly affected its toxic activity, which highlights the relevance of the assembly mechanism on toxicity. | ||
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| 650 | 4 | |a Cell Death | |
| 650 | 4 | |a Equinatoxin II | |
| 650 | 4 | |a Membrane Biophysics | |
| 650 | 4 | |a Membrane Protein | |
| 650 | 4 | |a Permeability | |
| 650 | 4 | |a Toxin | |
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