Videv Pavel, Mladenov Nikola, Andreeva Tonya, Mladenova Kirilka, Moskova-Doumanova Veselina, Nikolaev Georgi, Petrova Svetla D, Doumanov Jordan A
Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria.
Faculty of Medicine, Medical University-Sofia, 1 Sv. Georgi Sofiiski Str., 1431 Sofia, Bulgaria.
Membranes (Basel). 2021 Jan 13;11(1):52. doi: 10.3390/membranes11010052.
Human bestrophin-1 protein (hBest1) is a transmembrane channel associated with the calcium-dependent transport of chloride ions in the retinal pigment epithelium as well as with the transport of glutamate and GABA in nerve cells. Interactions between hBest1, sphingomyelins, phosphatidylcholines and cholesterol are crucial for hBest1 association with cell membrane domains and its biological functions. As cholesterol plays a key role in the formation of lipid rafts, motional ordering of lipids and modeling/remodeling of the lateral membrane structure, we examined the effect of different cholesterol concentrations on the surface tension of hBest1/POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and hBest1/SM Langmuir monolayers in the presence/absence of Ca ions using surface pressure measurements and Brewster angle microscopy studies. Here, we report that cholesterol: (1) has negligible condensing effect on pure hBest1 monolayers detected mainly in the presence of Ca ions, and; (2) induces a condensing effect on composite hBest1/POPC and hBest1/SM monolayers. These results offer evidence for the significance of intermolecular protein-lipid interactions for the conformational dynamics of hBest1 and its biological functions as multimeric ion channel.
人视紫红质-1蛋白（hBest1）是一种跨膜通道，与视网膜色素上皮细胞中氯离子的钙依赖性转运以及神经细胞中谷氨酸和γ-氨基丁酸的转运有关。hBest1、鞘磷脂、磷脂酰胆碱和胆固醇之间的相互作用对于hBest1与细胞膜结构域的结合及其生物学功能至关重要。由于胆固醇在脂筏的形成、脂质的运动有序性以及侧向膜结构的建模/重塑中起关键作用，我们使用表面压力测量和布鲁斯特角显微镜研究，研究了不同胆固醇浓度在有无钙离子存在的情况下对hBest1/POPC（1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱）和hBest1/SM朗缪尔单层膜表面张力的影响。在此，我们报告胆固醇：（1）对主要在钙离子存在下检测到的纯hBest1单层膜的凝聚作用可忽略不计；（2）对复合hBest1/POPC和hBest1/SM单层膜具有凝聚作用。这些结果为分子间蛋白质-脂质相互作用对hBest1构象动力学及其作为多聚体离子通道的生物学功能的重要性提供了证据。
