title: The [Het-s] prion of Podospora anserina and its role in heterokaryon incompatibility.
abstract: [Het-s] is a prion from the filamentous fungus Podospora anserina and corresponds to a self-perpetuating amyloid aggregate of the HET-s protein. This prion protein is involved in a fungal self/non-self discrimination process termed heterokaryon incompatibility corresponding to a cell death reaction occurring upon fusion of genetically unlike strains. Two antagonistic allelic variants of this protein exist: HET-s, the prion form of which corresponds to [Het-s] and HET-S, incapable of prion formation. Fusion of a [Het-s] and HET-S strain triggers the incompatibility reaction, so that interaction of HET-S with the [Het-s] prion leads to cell death. HET-s and HET-S are highly homologous two domain proteins with a N-terminal globular domain termed HeLo and a C-terminal unstructured prion forming domain (PFD). The structure of the prion form of the HET-s PFD has been solved by solid state NMR and corresponds to a very well ordered β-solenoid fold with a triangular hydrophobic core. The ability to form this β-solenoid fold is retained in a distant homolog of HET-s from another fungal species. A model for the mechanism of [Het-s]/HET-S incompatibility has been proposed. It is believe that when interacting with the [Het-s] prion seed, the HET-S C-terminal region adopts the β-solenoid fold. This would act as a conformational switch to induce refolding and activation of the HeLo domain which then would exert its toxicity by a yet unknown mechanism.
authors.affiliation: Non-self recognition in fungi, Institut de Biochimie et de Génétique Cellulaire, UMR 5095, CNRS-Université de Bordeaux 2, 1 rue Camille St Saens, Bordeaux cedex, France. sven.saupe@ibgc.u-bordeaux2.fr
authors.forename: Sven J
authors.initials: SJ
authors.lastname: Saupe
mesh_terms: D000483:Alleles; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008961:Models, Structural; D048468:Podospora / Q000737:chemistry* / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; C083891:HET-S protein, Podospora anserina; D011328:Prions