title: Signal transduction by a fungal NOD-like receptor based on propagation of a prion amyloid fold.
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.
authors: Non-self recognition in Fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS-Université de Bordeaux, Bordeaux, France.
authors: Asen
authors: A
authors: Daskalov
authors: Institute of Chemistry & Biology of Membranes & Nanoobjects, CNRS, CBMN, UMR 5248, Pessac, France.
authors: Birgit
authors: B
authors: Habenstein
authors: Institute of Chemistry & Biology of Membranes & Nanoobjects, CNRS, CBMN, UMR 5248, Pessac, France.
authors: Denis
authors: D
authors: Martinez
authors: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg, Wageningen, The Netherlands.
authors: Alfons J M
authors: AJ
authors: Debets
authors: Institut de Nanociència i nanotecnologia, Departament Fisicoquímica, Universitat de Barcelona, Joan XXIII s/n, Barcelona, Spain.
authors: Raimon
authors: R
authors: Sabaté
authors: Institute of Chemistry & Biology of Membranes & Nanoobjects, CNRS, CBMN, UMR 5248, Pessac, France.
authors: Antoine
authors: A
authors: Loquet
authors: Non-self recognition in Fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS-Université de Bordeaux, Bordeaux, France.
authors: Sven J
authors: SJ
authors: Saupe
mesh_terms: D020816:Amino Acid Motifs; D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008958:Models, Molecular; D008969:Molecular Sequence Data; D048468:Podospora / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D058227:Amyloidogenic Proteins; D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; D011328:Prions; D011956:Receptors, Cell Surface