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The assembly dynamics of the cytolytic pore toxin ClyA
Pore-forming toxins are protein assemblies used by many organisms to disrupt the membranes of target cells. They are expressed as soluble monomers that assemble spontaneously into multimeric pores. However, owing to their complexity, the assembly processes have not been resolved in detail for any po...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347018/ https://www.ncbi.nlm.nih.gov/pubmed/25652783 http://dx.doi.org/10.1038/ncomms7198 |
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author | Benke, Stephan Roderer, Daniel Wunderlich, Bengt Nettels, Daniel Glockshuber, Rudi Schuler, Benjamin |
author_facet | Benke, Stephan Roderer, Daniel Wunderlich, Bengt Nettels, Daniel Glockshuber, Rudi Schuler, Benjamin |
author_sort | Benke, Stephan |
collection | PubMed |
description | Pore-forming toxins are protein assemblies used by many organisms to disrupt the membranes of target cells. They are expressed as soluble monomers that assemble spontaneously into multimeric pores. However, owing to their complexity, the assembly processes have not been resolved in detail for any pore-forming toxin. To determine the assembly mechanism for the ring-shaped, homododecameric pore of the bacterial cytolytic toxin ClyA, we collected a diverse set of kinetic data using single-molecule spectroscopy and complementary techniques on timescales from milliseconds to hours, and from picomolar to micromolar ClyA concentrations. The entire range of experimental results can be explained quantitatively by a surprisingly simple mechanism. First, addition of the detergent n-dodecyl-β-D-maltopyranoside to the soluble monomers triggers the formation of assembly-competent toxin subunits, accompanied by the transient formation of a molten-globule-like intermediate. Then, all sterically compatible oligomers contribute to assembly, which greatly enhances the efficiency of pore formation compared with simple monomer addition. |
format | Online Article Text |
id | pubmed-4347018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43470182015-03-10 The assembly dynamics of the cytolytic pore toxin ClyA Benke, Stephan Roderer, Daniel Wunderlich, Bengt Nettels, Daniel Glockshuber, Rudi Schuler, Benjamin Nat Commun Article Pore-forming toxins are protein assemblies used by many organisms to disrupt the membranes of target cells. They are expressed as soluble monomers that assemble spontaneously into multimeric pores. However, owing to their complexity, the assembly processes have not been resolved in detail for any pore-forming toxin. To determine the assembly mechanism for the ring-shaped, homododecameric pore of the bacterial cytolytic toxin ClyA, we collected a diverse set of kinetic data using single-molecule spectroscopy and complementary techniques on timescales from milliseconds to hours, and from picomolar to micromolar ClyA concentrations. The entire range of experimental results can be explained quantitatively by a surprisingly simple mechanism. First, addition of the detergent n-dodecyl-β-D-maltopyranoside to the soluble monomers triggers the formation of assembly-competent toxin subunits, accompanied by the transient formation of a molten-globule-like intermediate. Then, all sterically compatible oligomers contribute to assembly, which greatly enhances the efficiency of pore formation compared with simple monomer addition. Nature Pub. Group 2015-02-05 /pmc/articles/PMC4347018/ /pubmed/25652783 http://dx.doi.org/10.1038/ncomms7198 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Benke, Stephan Roderer, Daniel Wunderlich, Bengt Nettels, Daniel Glockshuber, Rudi Schuler, Benjamin The assembly dynamics of the cytolytic pore toxin ClyA |
title | The assembly dynamics of the cytolytic pore toxin ClyA |
title_full | The assembly dynamics of the cytolytic pore toxin ClyA |
title_fullStr | The assembly dynamics of the cytolytic pore toxin ClyA |
title_full_unstemmed | The assembly dynamics of the cytolytic pore toxin ClyA |
title_short | The assembly dynamics of the cytolytic pore toxin ClyA |
title_sort | assembly dynamics of the cytolytic pore toxin clya |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347018/ https://www.ncbi.nlm.nih.gov/pubmed/25652783 http://dx.doi.org/10.1038/ncomms7198 |
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