ArticlePLoS biology2012
The mechanism of toxicity in HET-S/HET-s prion incompatibility.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 144 citations in OpenAlex.
- Regulated Cell Death in Fungi, the Role of Metacaspases and Assay Techniques.Methods and protocols · 2026Review
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- Harnessing deep learning for proteome-scale detection of amyloid signaling motifs.Bioinformatics (Oxford, England) · 2025Article
- A meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A structural rationale for reversible vs irreversible amyloid fibril formation from a single protein.Nature communications · 2024Article
- What are the 100 most cited fungal genera?Studies in mycology · 2024Article
- Wheat powdery mildew resistance gene Pm13 encodes a mixed lineage kinase domain-like protein.Nature communications · 2024Article
- Deep orange gene editing triggers temperature-sensitive lethal phenotypes in Ceratitis capitata.BMC biotechnology · 2024Article
- A Story Between s and S: [Het-s] Prion of the FungusMycobiology · 2024Review
- Amyloids and prions in the light of evolution.Current genetics · 2023Review
- Programmed Cell Death in Unicellular Versus Multicellular Organisms.Annual review of genetics · 2023Review
- A toxin-antidote system contributes to interspecific reproductive isolation in rice.Nature communications · 2023Article
- Emergence of the fungal immune system.iScience · 2023Review
- Article
- Exploring a diverse world of effector domains and amyloid signaling motifs in fungal NLR proteins.PLoS computational biology · 2022Article
- What makes functional amyloids work?Critical reviews in biochemistry and molecular biology · 2022Review
- The Cryo-EM structures of two amphibian antimicrobial cross-β amyloid fibrils.Nature communications · 2022Article
- The evolution of regulated cell death pathways in animals and their evasion by pathogens.Physiological reviews · 2022Review
- Molecular Mechanisms and Evolutionary Consequences of Spore Killers in Ascomycetes.Microbiology and molecular biology reviews : MMBR · 2021Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HET-s protein from the filamentous fungus Podospora anserina is a prion involved in a cell death reaction termed heterokaryon incompatibility. This reaction is observed at the point of contact between two genetically distinct strains when one harbors a HET-s prion (in the form of amyloid aggregates) and the other expresses a soluble HET-S protein (96% identical to HET-s). How the HET-s prion interaction with HET-S brings about cell death remains unknown; however, it was recently shown that this interaction leads to a relocalization of HET-S from the cytoplasm to the cell periphery and that this change is associated with cell death. Here, we present detailed insights into this mechanism in which a non-toxic HET-s prion converts a soluble HET-S protein into an integral membrane protein that destabilizes membranes. We observed liposomal membrane defects of approximately 10 up to 60 nm in size in transmission electron microscopy images of freeze-fractured proteoliposomes that were formed in mixtures of HET-S and HET-s amyloids. In liposome leakage assays, HET-S has an innate ability to associate with and disrupt lipid membranes and that this activity is greatly enhanced when HET-S is exposed to HET-s amyloids. Solid-state nuclear magnetic resonance (NMR) analyses revealed that HET-s induces the prion-forming domain of HET-S to adopt the β-solenoid fold (previously observed in HET-s) and this change disrupts the globular HeLo domain. These data indicate that upon interaction with a HET-s prion, the HET-S HeLo domain partially unfolds, thereby exposing a previously buried ∼34-residue N-terminal transmembrane segment. The liberation of this segment targets HET-S to the membrane where it further oligomerizes, leading to a loss of membrane integrity. HET-S thus appears to display features that are reminiscent of pore-forming toxins.
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