Zhai Xiuhong, Gao Yong-Guang, Mishra Shrawan K, Simanshu Dhirendra K, Boldyrev Ivan A, Benson Linda M, Bergen H Robert, Malinina Lucy, Mundy John, Molotkovsky Julian G, Patel Dinshaw J, Brown Rhoderick E
From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912,
From the Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
J Biol Chem. 2017 Feb 10;292(6):2531-2541. doi: 10.1074/jbc.M116.760256. Epub 2016 Dec 23.
Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants include mutant (). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, "soluble" phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1P glycolipid.
用于研究植物中阻止病原体感染传播和免疫反应激活的局部细胞自杀的遗传模型包括突变体（）。在这种突变体中，鞘脂稳态通过ACD11的消耗而被破坏，ACD11是一种对神经酰胺1-磷酸（C1P）和植物C1P具有特异性的脂质转移蛋白。ACD11和人神经酰胺-1-磷酸转移蛋白（CPTP）中的C1P结合位点被阳离子残基包围。在这里，我们研究了阴离子磷酸甘油酯对ACD11和CPTP的功能调节，发现C1P源囊泡中的1-棕榈酰-2-油酰-磷脂酸或1-棕榈酰-2-油酰-磷脂酰甘油（≤15摩尔%）抑制了C1P的膜间转移。相比之下，用1-棕榈酰-2-油酰-磷脂酰丝氨酸替代则刺激了ACD11和CPTP的C1P转移。值得注意的是，“可溶性”磷脂酰丝氨酸（二己酰磷脂酰丝氨酸）未能刺激C1P转移。此外，阴离子磷酸甘油酯均未影响人糖脂脂质转移蛋白（GLTP）的转移作用，GLTP对糖脂具有特异性，并且在其糖脂结合位点附近几乎没有阳离子残基。这些发现为任何GLTP折叠表面上存在潜在的磷酸甘油酯头部基团特异性调节相互作用位点提供了首个证据，并描绘了GLTP超家族成员之间对C1P糖脂具有特异性的新差异。
