Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold

A. Daskalov, B. Habenstein, D. Martinez, A.J.M. Debets, R. Sabate, A. Loquet, S.J. Saupe

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)

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 ß-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 ß-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 ß-solenoid fold. Here, we analyze the ability of NWD2 to induce formation of the ß-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 ß-solenoid fold abolish templating activity. In vitro, the N-terminal motif assembles into infectious prion amyloids that display a structure resembling the ß-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 ß-solenoid fold in fungal NLR function further highlights the general importance of amyloid and prion-like signaling in immunity-related cell fate pathways
Original languageEnglish
Article numbere1002059
JournalPloS Biology
Volume13
Issue number2
DOIs
Publication statusPublished - 2015

Keywords

  • het-s prion
  • state nmr-spectroscopy
  • non-self recognition
  • heterokaryon incompatibility gene
  • glycolipid transfer protein
  • podospora-anserina
  • vegetative incompatibility
  • cell-death
  • het-s(218-289) prion
  • diversity

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    Daskalov, A., Habenstein, B., Martinez, D., Debets, A. J. M., Sabate, R., Loquet, A., & Saupe, S. J. (2015). Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold. PloS Biology, 13(2), [e1002059]. https://doi.org/10.1371/journal.pbio.1002059