Curtin Medical School, Curtin Health Innovation Research Institute and Curtin Institute for Data Science, Curtin University, GPO Box U1987, Perth, WA 6845, Australia.
Curtin Medical School, Curtin Health Innovation Research Institute and Curtin Institute for Data Science, Curtin University, GPO Box U1987, Perth, WA 6845, Australia.
Biochim Biophys Acta Biomembr. 2023 Dec;1865(8):184201. doi: 10.1016/j.bbamem.2023.184201. Epub 2023 Aug 2.
Surface lipids influence the biological activities of high-density lipoproteins (HDLs) but their species-specific effects on HDL structure, dynamics, and surface interactome has remained unclear. Building upon the five-lipid species HDL models developed and characterised in previous work, representative models of the major HDL subpopulations found in human plasma containing apolipoprotein A-I (apoA-I) have been studied using molecular dynamics simulation to describe their varying degrees of surface lipidome complexity. Specifically, two additional sets of representative HDL subpopulation particles were developed, one with sphingomyelin (SM) and the other with SM, phosphatidylethanolamine, phosphatidylinositol, and ceramide in quantities reflecting average levels characterised for HDL subpopulations derived from normolipidemic patients. These lipid species were assessed in terms of HDL size, morphology, dynamics, and overall interactome. The findings reveal that the presence of a representative SM fraction marginally enhanced HDL interfacial curvature and surface monolayer rigidity, manifesting in tighter phospholipid packing and slower surface lipid dynamics relative to SM-deficient HDL models. Furthermore, the presence of SM resulted in a reduction in the solvent exposure of core lipids and cholesterol molecules, whilst also enhancing apolipoprotein conformational flexibility and its overall twisting across the HDL surface. The hydrophobicity of apoA-I-bound lipid patches and the proportion of apoA-I hydrophobic surface area is enhanced by the overall lipidation of apoA-I irrespective of lipid composition. These findings offer new insights into how the surface lipid composition of different HDL subpopulations can significantly impact the overall interactome of HDL particles, potentially influencing subpopulation-specific biological functions like lipid scavenging and receptor interactions.
表面脂质会影响高密度脂蛋白（HDL）的生物学活性，但它们对 HDL 结构、动态和表面相互作用组的具体影响仍不清楚。在之前工作中开发和表征的五种脂质 HDL 模型的基础上，使用分子动力学模拟研究了载有载脂蛋白 A-I (apoA-I) 的主要 HDL 亚群的代表性模型，以描述它们不同程度的表面脂质组复杂性。具体来说，开发了另外两组具有代表性的 HDL 亚群粒子，一组含有鞘磷脂 (SM)，另一组含有 SM、磷脂酰乙醇胺、磷脂酰肌醇和神经酰胺，其数量反映了从正常脂质患者中衍生的 HDL 亚群的平均水平。这些脂质种类从 HDL 的大小、形态、动力学和整体相互作用组等方面进行了评估。研究结果表明，代表性 SM 部分的存在略微增加了 HDL 界面曲率和表面单层刚性，与缺乏 SM 的 HDL 模型相比，表现为更紧密的磷脂包装和更慢的表面脂质动力学。此外，SM 的存在减少了核心脂质和胆固醇分子的溶剂暴露，同时增强了载脂蛋白的构象灵活性及其在整个 HDL 表面的整体扭曲。载脂蛋白 A-I 结合的脂质斑块的疏水性和载脂蛋白 A-I 疏水表面积的比例通过载脂蛋白 A-I 的整体脂化而增强，而与脂质组成无关。这些发现为不同 HDL 亚群的表面脂质组成如何显著影响 HDL 颗粒的整体相互作用组提供了新的见解，这可能会影响亚群特异性的生物学功能，如脂质清除和受体相互作用。
