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| Autori principali: | , |
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| Natura: | Recurso digital |
| Lingua: | |
| Pubblicazione: |
Zenodo
2025
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| Soggetti: | |
| Accesso online: | https://doi.org/10.5281/zenodo.15314712 |
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Sommario:
- <p>Caveolin-1 is a scaffolding protein crucial for the formation of caveolae, specialized membrane structures that are involved in diverse cellular processes such as endocytosis, mechano-sensing, and lipid regulation. Recently, a unique structure of the 8S oligomeric complex of caveolin-1 was resolved by cryo-electron microscopy, providing a foundational basis for understanding its molecular mechanisms. In this study, we probe the membrane interactions of the oligomeric caveolin-1 complex in membrane lipid bilayers and vesicles. We performed coarse-grain molecular dynamics simulations to delineate the interactions of the palmitoylated and non-palmitoylated caveolin-1 with multi-component membranes. During the simulations, the caveolin-1 complex binds to the membranes and remodels the membrane into a “bud-like” structure in bilayers, but not vesicles. Surprisingly, a similar mode of binding is observed in both bilayers and vesicles,<br>despite the differences in the induced curvature. A detailed analysis of palmitoyl tail interactions revealed a conformational transition upon membrane binding, indicating a step-wise mechanism by which caveolin-1 inserts into the lipid environment. Cholesterol and phosphoserine lipid enrichment, hallmarks of caveolin-1 binding, were observed in a membrane-topology dependent manner. The differential cholesterol clustering observed between vesicles and bilayers, highlights the curvature dependent nature of caveolin-1-mediated lipid organization. The significant positive curvature induced by caveolin-1 in bilayers underscores its potential role in membrane remodeling processes such as vesicle budding and endocytosis. Our<br>work highlights the dual significance of lipid organization and membrane topology in the functional dynamics of caveolin-1,shedding light on its role in inducing and sensing membrane curvature, which are pivotal for various cellular processes.</p>