Caveolins are lipid-binding proteins that can organize membrane remodeling and oligomerize into the 8S complex. The CAV1-8S complex comprises a disk-like structure, about 15 nm in diameter, with a central beta barrel. Further oligomerization of 8S complexes remodels the membrane into caveolae vessels, with a dependence on cholesterol concentration. However, the molecular mechanisms behind membrane remodeling and cholesterol filtering are still not understood. Performing atomistic molecular dynamics simulations in combination with advanced sampling techniques, we describe how the CAV1-8S complex bends the membrane and accumulates cholesterol. Here, our simulations show an enhancing effect by the palmitoylations of CAV1, and we predict that the CAV1-8S complex can extract cholesterol molecules from the lipid bilayer and accommodate them in its beta barrel. Through backmapping to the all-atom level, we also conclude that the Martini v.2 coarse-grained force field overestimates membrane bending, as the atomistic simulations exhibit only very localized bending.

中文翻译：

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Caveolin-1 复合物的脂质组织


Caveolin 是脂质结合蛋白，可以组织膜重塑并寡聚化成 8S 复合物。CAV1-8S 复合物由直径约 15 nm 的圆盘状结构组成，具有一个中央 β 桶。8S 复合物的进一步寡聚化将膜重塑为小窝血管，依赖于胆固醇浓度。然而，膜重塑和胆固醇过滤背后的分子机制仍不清楚。结合先进的采样技术进行原子分子动力学模拟，我们描述了 CAV1-8S 复合物如何弯曲膜并积累胆固醇。在这里，我们的模拟显示了 CAV1 棕榈酰化的增强作用，我们预测 CAV1-8S 复合物可以从脂质双层中提取胆固醇分子并将其容纳在其 β 桶中。通过回溯映射到全原子水平，我们还得出结论，Martini v.2 粗粒度力场高估了膜弯曲，因为原子模拟只表现出非常局部的弯曲。