Mechanisms of RCD-1 pore formation and membrane bending
Abstract Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elem...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56398-5 |
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| Summary: | Abstract Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds acidic lipid membranes, forms pores, and induces membrane bending. Using atomic force microscopy (AFM) and AlphaFold, we show that RCD-1-1 and RCD-1-2 form heterodimers that further self-assemble into ~14.5 nm-wide transmembrane pores (~10 heterodimers). Moreover, through AFM force spectroscopy and micropipette aspiration, we reveal that RCD-1 proteins bend membranes with low bending moduli. This combined action of pore formation and membrane deformation may constitute a conserved mechanism within the broader GSDM family. |
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| ISSN: | 2041-1723 |