Unit of Protein Crystallography and Structural Immunology, Navarrabiomed, 31008, Pamplona, Navarra, Spain.
Public University of Navarra (UPNA), 31008, Pamplona, Navarra, Spain.
Sci Rep. 2022 Sep 6;12(1):15127. doi: 10.1038/s41598-022-18844-y.
Evidence is mounting that the nature of the lipid bound to the endothelial cell protein C receptor (EPCR) has an impact on its biological roles, as observed in anticoagulation and more recently, in autoimmune disease. Phosphatidylethanolamine and phosphatidylcholine species dominate the EPCR lipid cargo, yet, the extent of diversity in the EPCR-associated lipid repertoire is still unknown and remains to be uncovered. We undertook mass spectrometry analyses to decipher the EPCR lipidome, and identified species not yet described as EPCR ligands, such as phosphatidylinositols and phosphatidylserines. Remarkably, we found further, more structurally divergent lipids classes, represented by ceramides and sphingomyelins, both in less abundant quantities. In support of our mass spectrometry results and previous studies, high-resolution crystal structures of EPCR in three different space groups point to a prevalent diacyl phospholipid moiety in EPCR's pocket but a mobile and ambiguous lipid polar head group. In sum, these studies indicate that EPCR can associate with varied lipid classes, which might impact its properties in anticoagulation and the onset of autoimmune disease.
越来越多的证据表明，内皮细胞蛋白 C 受体 (EPCR) 结合的脂质的性质对其生物学功能有影响，这在抗凝和最近的自身免疫性疾病中都有观察到。磷脂酰乙醇胺和磷脂酰胆碱是 EPCR 脂质货物的主要成分，但 EPCR 相关脂质谱的多样性程度仍不清楚，有待进一步揭示。我们进行了质谱分析来破译 EPCR 的脂质组，发现了一些尚未被描述为 EPCR 配体的物质，如磷脂酰肌醇和磷脂酰丝氨酸。值得注意的是，我们还发现了更多结构上更为不同的脂质类，如神经酰胺和鞘磷脂，其丰度较低。这些研究支持了我们的质谱结果和以前的研究，三种不同空间群的 EPCR 的高分辨率晶体结构表明 EPCR 口袋中存在普遍的二酰基磷脂部分，但脂质极性头部基团是可移动和不确定的。总之，这些研究表明，EPCR 可以与多种脂质类结合，这可能影响其在抗凝和自身免疫性疾病中的作用。
