Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/106928
Title: Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold
Author: Daskalov, Asen
Habenstein, Birgi
Martinez, Denis
Debets, Alfons J. M.
Sabaté Lagunas, Raimon
Loquet, Antoine
Saupe, Sven J.
Keywords: Proteïnes
Prions
Amiloïdosi
Proteins
Prions
Amyloidosis
Issue Date: 11-Feb-2015
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1371/journal.pbio.1002059
It is part of: PLoS Biology, 2015, vol. 13, num. 2, p. e1002059
Related resource: https://doi.org/10.1371/journal.pbio.1002059
URI: http://hdl.handle.net/2445/106928
ISSN: 1544-9173
Appears in Collections:Articles publicats en revistes (Institut de Nanociència i Nanotecnologia (IN2UB))
Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

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