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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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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| author | Keli Ren James Daniel Farrell Yueyue Li Xinrui Guo Ruipei Xie Xin Liu Qiaozhen Kang Qihui Fan Fangfu Ye Jingjin Ding Fang Jiao |
| author_facet | Keli Ren James Daniel Farrell Yueyue Li Xinrui Guo Ruipei Xie Xin Liu Qiaozhen Kang Qihui Fan Fangfu Ye Jingjin Ding Fang Jiao |
| author_sort | Keli Ren |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1a23f79e19a74092b320e3a2471a5f77 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1a23f79e19a74092b320e3a2471a5f772025-01-26T12:42:36ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-025-56398-5Mechanisms of RCD-1 pore formation and membrane bendingKeli Ren0James Daniel Farrell1Yueyue Li2Xinrui Guo3Ruipei Xie4Xin Liu5Qiaozhen Kang6Qihui Fan7Fangfu Ye8Jingjin Ding9Fang Jiao10Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesSchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41467-025-56398-5 |
| spellingShingle | Keli Ren James Daniel Farrell Yueyue Li Xinrui Guo Ruipei Xie Xin Liu Qiaozhen Kang Qihui Fan Fangfu Ye Jingjin Ding Fang Jiao Mechanisms of RCD-1 pore formation and membrane bending Nature Communications |
| title | Mechanisms of RCD-1 pore formation and membrane bending |
| title_full | Mechanisms of RCD-1 pore formation and membrane bending |
| title_fullStr | Mechanisms of RCD-1 pore formation and membrane bending |
| title_full_unstemmed | Mechanisms of RCD-1 pore formation and membrane bending |
| title_short | Mechanisms of RCD-1 pore formation and membrane bending |
| title_sort | mechanisms of rcd 1 pore formation and membrane bending |
| url | https://doi.org/10.1038/s41467-025-56398-5 |
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