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Direct Transmembrane Interaction between Actin and the Pore-Competent, Cholesterol-Dependent Cytolysin Pneumolysin

Please always quote using this URN: urn:nbn:de:bvb:20-opus-132297
  • The eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells. These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover. Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhanceThe eukaryotic actin cytoskeleton is an evolutionarily well-established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells. These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover. Here, we show that the pore-forming, cholesterol-dependent cytolysin pneumolysin (PLY), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro. In cells, the toxin co-localised with F-actin shortly after exposure, and this direct interaction was verified by Förster resonance energy transfer. PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved. The dissociation constant of G-actin binding to PLY in a biochemical environment was 170–190 nM, which is indicative of a high-affinity interaction, comparable to the affinity of other intracellular actin-binding factors. Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought.show moreshow less

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Metadaten
Author: Sabrina Hupp, Christina Förtsch, Carolin Wippel, Jiangtao Ma, Timothy J. Mitchell, Asparouh I. Iliev
URN:urn:nbn:de:bvb:20-opus-132297
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):Journal of Molecular Biology
Year of Completion:2013
Volume:425
Issue:3
Pagenumber:636-646
Source:Journal of Molecular Biology (2013) 425, 636–646. DOI:10.1016/j.jmb.2012.11.034
DOI:https://doi.org/10.1016/j.jmb.2012.11.034
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 615 Pharmakologie, Therapeutik
Tag:actin; cholesterol-dependent cytolysin; membrane; pneumolysin; pore-forming toxin
Release Date:2016/06/11
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung