Daskalov, AsenHabenstein, BirgiMartínez, DenisDebets, Alfons J. M.Sabaté Lagunas, RaimonLoquet, AntoineSaupe, Sven J.2017-02-142017-02-142015-02-111544-9173https://hdl.handle.net/2445/106928In 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.application/pdfengcc-by (c) Daskalov, Asen et al., 2015http://creativecommons.org/licenses/by/3.0/esProteïnesPrionsAmiloïdosiProteinsPrionsAmyloidosisinfo:eu-repo/semantics/article6473172017-02-14info:eu-repo/semantics/openAccess25671553