Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, Illinois.
Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, Illinois.
Biophys J. 2024 Nov 5;123(21):3688-3697. doi: 10.1016/j.bpj.2024.09.018. Epub 2024 Sep 20.
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.
窖蛋白是一种可以组织膜重塑并寡聚形成 8S 复合物的脂结合蛋白。CAV1-8S 复合物由一个直径约 15nm 的盘状结构组成，其中央有一个β桶。进一步的 8S 复合物寡聚化将膜重塑成 caveolae 小泡，这依赖于胆固醇浓度。然而，膜重塑和胆固醇过滤的分子机制仍不清楚。通过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 CAV1 的棕榈酰化具有增强作用，并且我们预测 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。通过回溯到全原子水平，我们还得出结论，Martini v.2 粗粒化力场高估了膜的弯曲，因为原子模拟仅显示非常局部的弯曲。
