National Chemical Laboratory, Council of Scientific and Industrial Research, Dr. Homi Bhabha Road, Pune 411008, India.
J Phys Chem B. 2012 Dec 20;116(50):14556-64. doi: 10.1021/jp3077886. Epub 2012 Dec 10.
Caveolin-1 (cav-1) is an important membrane protein that plays a vital role in cellular signaling and trafficking by organizing membrane domains. The peptide interacts with cholesterol-rich membranes and induces large morphological changes in them, forming microdomains such as caveolae. Here, we use coarse-grain molecular dynamics simulations to study the interaction of cav-1 peptides with several model bilayer systems mimicking biological scenarios, such as cholesterol-rich domains, cholesterol-depleted domains, and unsaturated lipid domains. We show that cholesterol modulates the depth as well as orientation of cav-1 binding to membranes. Furthermore, the presence of cholesterol stabilizes more open conformations of cav-1, and we speculate that the binding modes and open conformations could be responsible for inducing morphological changes in the bilayer. We also calculated the partitioning free energy to different bilayers and show that binding to cholesterol-rich bilayers is more favorable than cholesterol-depleted bilayers and the binding to unsaturated bilayers is the least favorable. Binding to cholesterol-rich bilayers also changes the pressure profile of the bilayer to which it is bound and thereby affects the local spontaneous curvature. Our results highlight molecular details of protein-lipid interplay and provide new insights into the effects of cav-1 in tuning the morphology of cholesterol-rich membranes.
窖蛋白-1（cav-1）是一种重要的膜蛋白，通过组织膜域在细胞信号转导和运输中起着至关重要的作用。该肽与富含胆固醇的膜相互作用，并诱导它们发生大的形态变化，形成微域，如小窝。在这里，我们使用粗粒分子动力学模拟来研究 cav-1 肽与几种模拟生物场景的模型双层系统的相互作用，如富含胆固醇的域、胆固醇耗尽的域和不饱和脂质域。我们表明胆固醇调节 cav-1 与膜结合的深度和方向。此外，胆固醇的存在稳定了 cav-1 的更多开放构象，我们推测结合模式和开放构象可能负责诱导双层的形态变化。我们还计算了不同双层的分区自由能，并表明与富含胆固醇的双层结合比与胆固醇耗尽的双层结合更有利，而与不饱和双层的结合最不利。与富含胆固醇的双层结合也改变了与其结合的双层的压力分布，从而影响局部自发曲率。我们的结果突出了蛋白质-脂质相互作用的分子细节，并为 cav-1 调节富含胆固醇的膜形态的作用提供了新的见解。
