Oka K, Ishimura-Oka K, Chu M J, Sullivan M, Krushkal J, Li W H, Chan L
Department of Cell Biology and Medicine, Baylor College of Medicine, Houston, Texas 77030.
Eur J Biochem. 1994 Sep 15;224(3):975-82. doi: 10.1111/j.1432-1033.1994.00975.x.
The very-low-density-lipoprotein receptor (VLDLR) is a recently described lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor (LDLR). This receptor has been suggested to be important for the metabolism of apoprotein-E-containing triacylglycerol-rich lipoproteins, such as very-low-density-lipoprotein (VLDL), beta-migrating VLDL and intermediate-density lipoprotein. cDNA clones that code for the VLDLR were isolated from a mouse heart cDNA library. The deduced amino acid sequence predicts a mature protein of 846 amino acids preceded by a 27-residue signal peptide. Three mRNA species for the VLDLR with sizes of 3.9, 4.5 and 7.9 kilobases were present in high concentration in heart and muscle, which utilize triacylglycerols as an energy source. VLDLR mRNA is also detected in decreasing amounts in kidney, brain, ovary, testis, lung and adipose tissue. It is essentially absent in liver and small intestine. The amino acid sequence of the VLDLR is highly conserved among rabbit, human and mouse. VLDLR contains five structural domains very similar to those in LDLR, except that the ligand-binding domain in VLDLR has an eightfold repeat instead of a sevenfold repeat in LDLR. Sequence conservation among animal species is much higher for the VLDLR than the LDLR. Sequences of the VLDLR from three vertebrate species and the LDLR from five vertebrate species were aligned and a phylogenetic tree was reconstructed. Although both receptors contain five domains and share amino acid sequence similarity, our computations showed that they diverged before the divergence between mammals and amphibians. In addition, sequence comparison of both receptor sequences suggests that the rabbit is evolutionarily closer to man than to the mouse. These results are consistent with the hypothesis that the VLDLR and the LDLR have evolved from a common ancestral gene to play distinct roles in lipoprotein metabolism and that the metabolic handling of triacylglycerol by the body via the VLDLR is a highly conserved mechanism.
极低密度脂蛋白受体（VLDLR）是一种最近被描述的脂蛋白受体，与低密度脂蛋白受体（LDLR）有相当大的相似性。有人认为该受体对含载脂蛋白E的富含三酰甘油的脂蛋白的代谢很重要，如极低密度脂蛋白（VLDL）、β-迁移VLDL和中间密度脂蛋白。编码VLDLR的cDNA克隆是从小鼠心脏cDNA文库中分离出来的。推导的氨基酸序列预测有一个由27个残基信号肽引导的846个氨基酸的成熟蛋白。VLDLR的三种mRNA种类，大小分别为3.9、4.5和7.9千碱基，在以三酰甘油为能量来源的心脏和肌肉中高度富集。在肾脏、大脑、卵巢、睾丸、肺和脂肪组织中也能检测到含量逐渐减少的VLDLR mRNA。在肝脏和小肠中基本不存在。VLDLR的氨基酸序列在兔、人和小鼠之间高度保守。VLDLR包含五个与LDLR非常相似的结构域，只是VLDLR中的配体结合结构域有一个八重重复，而LDLR中有一个七重重复。VLDLR在动物物种间的序列保守性比LDLR高得多。对三种脊椎动物物种的VLDLR序列和五种脊椎动物物种的LDLR序列进行比对，并重建了系统发育树。尽管这两种受体都包含五个结构域并具有氨基酸序列相似性，但我们的计算表明它们在哺乳动物和两栖动物分化之前就已经分化。此外，两种受体序列的比较表明，兔子在进化上与人类比与小鼠更接近。这些结果与以下假设一致：VLDLR和LDLR从一个共同的祖先基因进化而来，在脂蛋白代谢中发挥不同的作用，并且身体通过VLDLR对三酰甘油的代谢处理是一种高度保守的机制。
