Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes.
Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes.
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DOI：
10.15698/mic2018.02.614
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发表时间：
2017-12-28
期刊：
影响因子：
--
通讯作者：
Levine T
中科院分区：
文献类型：
--
作者：
Hayes M;Choudhary V;Ojha N;Shin JJ;Han GS;Carman GM;Loewen CJ;Prinz WA;Levine T
脂肪储存诱导跨膜蛋白(FIT或FITM)与三酰甘油向脂滴的分配和内质网中脂滴的萌发有关。在分子水平上，唯一相关的相互作用是FITM直接与三酰甘油和二酰甘油结合，但它们在分子水平上如何发挥作用尚不清楚。酿酒酵母有两个FITM同源物：Scs3p和Yft2p。Scs3p最初被识别是因为缺失导致肌醇营养不良，对添加胆碱具有异常的敏感性。这有力地表明了Scs3p在磷脂生物合成中的作用。尽可能广泛地研究FITM家族，我们发现FITM广泛存在于真核生物中，这表明FITM存在于真核生物的最后一个共同祖先中。蛋白质序列比对还表明，FITM序列包含脂质磷酸酶/磷酸转移酶(LPT)酶的活性部位。这个大家庭将含有磷酸盐的头基在脂类之间转移，或者用水来交换。我们证实了FITM与LPTs相关的预测，因为我们证明了当FITM过度表达时，假定催化位点上的单一氨基酸取代阻止了它们在低肌醇/高胆碱介质中拯救突变体的生长的能力。这些替换还阻止了与酵母中FITM缺失相关的其他表型的挽救，包括Opi1p的错误定位、内质网形态缺陷和异常的脂滴发芽。这些结果表明，Scs3p、Yft2p和FITM一般都是LPT酶，参与了磷脂代谢的一个未知的关键步骤。
Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT) enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism.
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作者：
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通讯作者：
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
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DOI：
10.1083/jcb.201505067
发表时间：
2015-10-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Choudhary V;Ojha N;Golden A;Prinz WA
通讯作者：
Prinz WA