Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3
Abstract Gasdermin D and gasdermin A3 belong to the same family of pore-forming proteins and executors of pyroptosis, a form of programmed cell death. To unveil the process of their pore formation, we examine the energy landscapes upon insertion of the gasdermin D and A3 monomers into a lipid bilaye...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01400-2 |
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| author | Viktoria Korn Kristyna Pluhackova |
| author_facet | Viktoria Korn Kristyna Pluhackova |
| author_sort | Viktoria Korn |
| collection | DOAJ |
| description | Abstract Gasdermin D and gasdermin A3 belong to the same family of pore-forming proteins and executors of pyroptosis, a form of programmed cell death. To unveil the process of their pore formation, we examine the energy landscapes upon insertion of the gasdermin D and A3 monomers into a lipid bilayer by extensive atomistic molecular dynamics simulations. We reveal a lower free energy barrier of membrane insertion for gasdermin D than for gasdermin A3 and a preference of gasdermin D for the membrane-inserted and of gasdermin A3 for the membrane-adsorbed state, suggesting that gasdermin D first inserts and then oligomerizes while gasdermin A3 oligomerizes and then inserts. Gasdermin D stabilizes itself in the membrane by forming more salt bridges and pulling phosphatidylethanolamine lipids and more water into the membrane. Gasdermin-lipid interactions support the pore formation. Our findings suggest that both the gasdermin species and the lipid composition modulate gasdermin pore formation. |
| format | Article |
| id | doaj-art-2cc9b35ded104a909c111ed47ef7d035 |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-2cc9b35ded104a909c111ed47ef7d0352025-02-09T12:16:25ZengNature PortfolioCommunications Chemistry2399-36692025-02-018111310.1038/s42004-024-01400-2Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3Viktoria Korn0Kristyna Pluhackova1Stuttgart Center for Simulation Science, Cluster of Excellence EXC 2075, University of StuttgartStuttgart Center for Simulation Science, Cluster of Excellence EXC 2075, University of StuttgartAbstract Gasdermin D and gasdermin A3 belong to the same family of pore-forming proteins and executors of pyroptosis, a form of programmed cell death. To unveil the process of their pore formation, we examine the energy landscapes upon insertion of the gasdermin D and A3 monomers into a lipid bilayer by extensive atomistic molecular dynamics simulations. We reveal a lower free energy barrier of membrane insertion for gasdermin D than for gasdermin A3 and a preference of gasdermin D for the membrane-inserted and of gasdermin A3 for the membrane-adsorbed state, suggesting that gasdermin D first inserts and then oligomerizes while gasdermin A3 oligomerizes and then inserts. Gasdermin D stabilizes itself in the membrane by forming more salt bridges and pulling phosphatidylethanolamine lipids and more water into the membrane. Gasdermin-lipid interactions support the pore formation. Our findings suggest that both the gasdermin species and the lipid composition modulate gasdermin pore formation.https://doi.org/10.1038/s42004-024-01400-2 |
| spellingShingle | Viktoria Korn Kristyna Pluhackova Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 Communications Chemistry |
| title | Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 |
| title_full | Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 |
| title_fullStr | Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 |
| title_full_unstemmed | Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 |
| title_short | Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3 |
| title_sort | vastly different energy landscapes of the membrane insertions of monomeric gasdermin d and a3 |
| url | https://doi.org/10.1038/s42004-024-01400-2 |
| work_keys_str_mv | AT viktoriakorn vastlydifferentenergylandscapesofthemembraneinsertionsofmonomericgasdermindanda3 AT kristynapluhackova vastlydifferentenergylandscapesofthemembraneinsertionsofmonomericgasdermindanda3 |