Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold.
In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s β-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-fo...
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doaj-62eda14e37c743e9b2f9009d4d0c791e2021-07-02T17:19:52ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852015-02-01132e100205910.1371/journal.pbio.1002059Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold.Asen DaskalovBirgit HabensteinDenis MartinezAlfons J M DebetsRaimon SabatéAntoine LoquetSven J SaupeIn the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s β-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-forming domain. The gene immediately adjacent to het-S encodes NWD2, a Nod-like receptor (NLR) with an N-terminal motif similar to the elementary repeat unit of the β-solenoid fold. NLRs are immune receptors controlling cell death and host defense processes in animals, plants and fungi. We have proposed that, analogously to [Het-s], NWD2 can activate the HET-S pore-forming protein by converting its prion-forming region into the β-solenoid fold. Here, we analyze the ability of NWD2 to induce formation of the β-solenoid prion fold. We show that artificial NWD2 variants induce formation of the [Het-s] prion, specifically in presence of their cognate ligands. The N-terminal motif is responsible for this prion induction, and mutations predicted to affect the β-solenoid fold abolish templating activity. In vitro, the N-terminal motif assembles into infectious prion amyloids that display a structure resembling the β-solenoid fold. In vivo, the assembled form of the NWD2 N-terminal region activates the HET-S pore-forming protein. This study documenting the role of the β-solenoid fold in fungal NLR function further highlights the general importance of amyloid and prion-like signaling in immunity-related cell fate pathways.https://doi.org/10.1371/journal.pbio.1002059 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Asen Daskalov Birgit Habenstein Denis Martinez Alfons J M Debets Raimon Sabaté Antoine Loquet Sven J Saupe |
spellingShingle |
Asen Daskalov Birgit Habenstein Denis Martinez Alfons J M Debets Raimon Sabaté Antoine Loquet Sven J Saupe Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. PLoS Biology |
author_facet |
Asen Daskalov Birgit Habenstein Denis Martinez Alfons J M Debets Raimon Sabaté Antoine Loquet Sven J Saupe |
author_sort |
Asen Daskalov |
title |
Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. |
title_short |
Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. |
title_full |
Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. |
title_fullStr |
Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. |
title_full_unstemmed |
Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold. |
title_sort |
signal transduction by a fungal nod-like receptor based on propagation of a prion amyloid fold. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2015-02-01 |
description |
In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s β-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-forming domain. The gene immediately adjacent to het-S encodes NWD2, a Nod-like receptor (NLR) with an N-terminal motif similar to the elementary repeat unit of the β-solenoid fold. NLRs are immune receptors controlling cell death and host defense processes in animals, plants and fungi. We have proposed that, analogously to [Het-s], NWD2 can activate the HET-S pore-forming protein by converting its prion-forming region into the β-solenoid fold. Here, we analyze the ability of NWD2 to induce formation of the β-solenoid prion fold. We show that artificial NWD2 variants induce formation of the [Het-s] prion, specifically in presence of their cognate ligands. The N-terminal motif is responsible for this prion induction, and mutations predicted to affect the β-solenoid fold abolish templating activity. In vitro, the N-terminal motif assembles into infectious prion amyloids that display a structure resembling the β-solenoid fold. In vivo, the assembled form of the NWD2 N-terminal region activates the HET-S pore-forming protein. This study documenting the role of the β-solenoid fold in fungal NLR function further highlights the general importance of amyloid and prion-like signaling in immunity-related cell fate pathways. |
url |
https://doi.org/10.1371/journal.pbio.1002059 |
work_keys_str_mv |
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