TY  - JOUR
A1  - Hupp, Sabrina
A1  - Förtsch, Christina
A1  - Wippel, Carolin
A1  - Ma, Jiangtao
A1  - Mitchell, Timothy J.
A1  - Iliev, Asparouh I.
T1  - Direct Transmembrane Interaction between Actin and the Pore-Competent, Cholesterol-Dependent Cytolysin Pneumolysin
T2  - Journal of Molecular Biology
N2  - 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 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.
KW  - pore-forming toxin
KW  - cholesterol-dependent cytolysin
KW  - actin
KW  - membrane
KW  - pneumolysin
Y1  - 2013
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/13229
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-132297
VL  - 425
IS  - 3
ER  -