National Chemical Laboratory, Council of Scientific and Industrial Research, Dr. Homi Bhabha Road, Pune 411008, India.
J Phys Chem B. 2020 Jun 25;124(25):5177-5185. doi: 10.1021/acs.jpcb.0c02962. Epub 2020 Jun 15.
The caveolin-1 (cav-1) protein is an integral component of caveolae and has been reported to colocalize with cholesterol and sphingomyelin-rich curved membrane domains. Here, we analyze the molecular interactions between cav-1 and sphingomyelin containing bilayers using a series of coarse-grain simulations, focusing on lipid clustering and membrane curvature. We considered a palmitoylated-cav-1 construct interacting with phospholipid/cholesterol membranes with asymmetrically distributed sphingomyelin, varying between 5 and 15% in total. We observe that cav-1 binds to the intracellular leaflet and induces a small positive curvature in the leaflet to which it is bound and an opposing negative curvature in the extracellular leaflet. Both cholesterol and sphingomyelin are observed to cluster in cav-1 bound membranes, mainly in the extracellular leaflet. Due to their negative spontaneous curvature, clustering of cholesterol and sphingomyelin facilitates membrane curvature such that the extent of either cholesterol or sphingomyelin clustering is dependent on the curvature induced. Our results suggest that cav-1 binding induces concentration-dependent curvature effects in sphingomyelin-rich membranes. Overall, our work is an important step in understanding the molecular basis of curvature and lipid clustering in cav-1 bound cellular membranes.
窖蛋白-1（cav-1）蛋白是质膜窖的组成部分，已报道其与胆固醇和鞘磷脂丰富的弯曲膜域共定位。在这里，我们使用一系列粗粒度模拟来分析 cav-1 与含有鞘磷脂的双层之间的分子相互作用，重点关注脂质聚集和膜曲率。我们考虑了与磷脂/胆固醇膜相互作用的棕榈酰化 cav-1 结构，其中鞘磷脂的分布不对称，总含量在 5%到 15%之间变化。我们观察到 cav-1 结合到胞质小叶，并在其结合的小叶中诱导小的正曲率，在细胞外小叶中诱导相反的负曲率。胆固醇和鞘磷脂都观察到在 cav-1 结合的膜中聚集，主要在细胞外小叶中。由于它们的负自发曲率，胆固醇和鞘磷脂的聚集促进了膜曲率，使得胆固醇或鞘磷脂聚集的程度取决于诱导的曲率。我们的结果表明，cav-1 结合在富含鞘磷脂的膜中诱导浓度依赖性的曲率效应。总的来说，我们的工作是理解 cav-1 结合的细胞质膜中曲率和脂质聚集的分子基础的重要一步。
