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PLoS Biol. 2015 Feb 11;13(2):e1002059. doi: 10.1371/journal.pbio.1002059. eCollection 2015 Feb.

Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold.

Author information

1
Non-self recognition in Fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS-Université de Bordeaux, Bordeaux, France.
2
Institute of Chemistry & Biology of Membranes & Nanoobjects, CNRS, CBMN, UMR 5248, Pessac, France.
3
Laboratory of Genetics, Wageningen University, Droevendaalsesteeg, Wageningen, The Netherlands.
4
Institut de Nanociència i nanotecnologia, Departament Fisicoquímica, Universitat de Barcelona, Joan XXIII s/n, Barcelona, Spain.

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.

PMID:
25671553
PMCID:
PMC4344463
DOI:
10.1371/journal.pbio.1002059
[Indexed for MEDLINE]
Free PMC Article

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