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甲基化磷脂酰乙醇胺衍生物对信号磷脂酸电离性质的影响。

The effect of methylated phosphatidylethanolamine derivatives on the ionization properties of signaling phosphatidic acid.

机构信息

Department of Biological Sciences, Kent State University, P.O. Box 5190, Kent, OH 44242, USA.

Department of Chemistry & Biochemistry, Kent State University, P.O. Box 5190, Kent, OH 44242, USA.

出版信息

Biophys Chem. 2023 May;296:107005. doi: 10.1016/j.bpc.2023.107005. Epub 2023 Mar 11.

DOI:10.1016/j.bpc.2023.107005
PMID:36934676
Abstract

Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) are the most abundant glycerophospholipids in eukaryotic membranes. The differences in the physicochemical properties of their headgroups have contrasting modulatory effects on their interaction with intracellular macromolecules. As such, their overall impact on membrane structure and function differs significantly. Enzymatic methylation of PE's amine headgroup produces two methylated derivatives namely monomethyl PE (MMPE) and dimethyl PE (DMPE) which have physicochemical properties that generally range between that of PE and PC. Additionally, their influence on membrane properties differs from both PE and PC. Although variations in headgroup methylation have been reported to affect signaling pathways, the direct influence that these differences exert on the ionization properties of signaling phospholipids have not been investigated. Here, we briefly review membrane function and structure that are mediated by the differences in headgroup methylation between PE, MMPE, DMPE and PC. In addition, using P MAS NMR, we investigate the effect of these four phospholipids on the ionization properties of the ubiquitous signaling anionic lipid phosphatidic acid (PA). Our results show that PA's ionization properties are differentially affected by changes in phospholipid headgroup methylation. This could have important implications for PA-protein binding and hence physiological functions in cells where signaling events lead to changes in abundance of methylated PE derivatives in the membrane.

摘要

磷脂酰乙醇胺 (PE) 和磷脂酰胆碱 (PC) 是真核细胞膜中含量最丰富的甘油磷脂。它们头部基团的物理化学性质的差异对其与细胞内大分子的相互作用有相反的调节作用。因此,它们对膜结构和功能的总体影响有很大的不同。PE 的胺基头部基团的酶促甲基化产生两种甲基化衍生物,即单甲基 PE (MMPE) 和二甲基 PE (DMPE),它们的物理化学性质通常介于 PE 和 PC 之间。此外,它们对膜性质的影响与 PE 和 PC 不同。尽管头部基团甲基化的变化已被报道会影响信号通路,但这些差异对信号磷脂离子化性质的直接影响尚未得到研究。在这里,我们简要回顾了由 PE、MMPE、DMPE 和 PC 头部基团甲基化差异介导的膜功能和结构。此外,我们使用 P MAS NMR 研究了这四种磷脂对普遍存在的信号阴离子脂质磷脂酸 (PA) 的离子化性质的影响。我们的结果表明,PA 的离子化性质因磷脂头部基团甲基化的变化而不同。这对于 PA-蛋白结合以及信号事件导致膜中甲基化 PE 衍生物丰度变化的细胞中的生理功能可能具有重要意义。

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