Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czechia.
Institute of Physics, Polish Academy of Sciences, Warsaw, Poland.
Commun Biol. 2024 Nov 27;7(1):1585. doi: 10.1038/s42003-024-07301-3.
Homeostasis of cellular membranes is maintained by fine-tuning their lipid composition. Yeast lipid transporter Osh6, belonging to the oxysterol-binding protein-related proteins family, was found to participate in the transport of phosphatidylserine (PS). PS synthesized in the endoplasmic reticulum is delivered to the plasma membrane, where it is exchanged for phosphatidylinositol 4-phosphate (PI4P). PI4P provides the driving force for the directed PS transport against its concentration gradient. In this study, we employed an in vitro approach to reconstitute the transport process into the minimalistic system of large unilamellar vesicles to reveal its fundamental biophysical determinants. Our study draws a comprehensive portrait of the interplay between the structure and dynamics of Osh6, the carried cargo lipid, and the physical properties of the involved membranes, with particular attention to the presence of charged lipids and to membrane fluidity. Specifically, we address the role of the cargo lipid, which, by occupying the transporter, imposes changes in its dynamics and, consequently, predisposes the cargo to disembark in the correct target membrane.
细胞膜的动态平衡是通过精细调节其脂质组成来维持的。酵母脂质转运蛋白 Osh6 属于甾醇结合蛋白相关蛋白家族，被发现参与磷脂酰丝氨酸 (PS) 的转运。内质网中合成的 PS 被运送到质膜，在那里它被交换为磷脂酰肌醇 4-磷酸 (PI4P)。PI4P 为 PS 的定向运输提供了驱动力，克服了其浓度梯度。在这项研究中，我们采用体外方法将运输过程重组到大型单层囊泡的最小系统中，以揭示其基本的生物物理决定因素。我们的研究描绘了 Osh6 的结构和动力学、携带的脂质货物以及所涉及膜的物理性质之间的相互作用的综合图景，特别关注带电荷脂质的存在和膜流动性。具体来说，我们研究了货物脂质的作用，货物脂质通过占据转运蛋白，引起其动力学变化，从而使货物更容易在正确的靶膜中脱离。
