Bernlohr D A, Simpson M A, Hertzel A V, Banaszak L J
Department of Biochemistry, College of Biological Sciences, Institute of Human Genetics, Medical School, University of Minnesota, St. Paul 55108-1022, USA.
Annu Rev Nutr. 1997;17:277-303. doi: 10.1146/annurev.nutr.17.1.277.
Intracellular lipid-binding proteins are a family of low-molecular-weight single-chain polypeptides that form 1:1 complexes with fatty acids, retinoids, or other hydrophobic ligands. These proteins are products of a large multigene family of unlinked loci distributed throughout the genome. Each lipid-binding protein exhibits a distinctive pattern of tissue distribution. Transcriptional control, regulated by a combination of peroxisome proliferator activated receptors and CCAAT/enhancer-binding proteins, allows for a variety of both cell and tissue-specific expression patterns. In some cells, fatty acids increase the expression of the lipid-binding protein genes. Fatty acids, or their metabolites, are activators of the peroxisome proliferator-activated receptor family of transcription factors. Therefore, as the concentration of lipid in the diet increases, the expression of lipid-binding proteins coordinately increases. As revealed by X-ray crystallography, the lipid-binding proteins fold into beta-barrels, forming a large internal water-filled cavity. Fatty acid ligands are bound within the cavity, occupying only about one-third of the accessible volume. The bound fatty acid is stabilized via a combination of enthalpic and entropic forces that govern ligand affinity and selectivity. Cytoplasmic lipid-binding proteins are the intracellular receptors for hydrophobic ligands, delivering them to the appropriate site for use as metabolic fuels and regulatory agents.
细胞内脂质结合蛋白是一类低分子量单链多肽，可与脂肪酸、类视黄醇或其他疏水配体形成1:1复合物。这些蛋白是分布于整个基因组中多个不连锁基因座的一个大型多基因家族的产物。每种脂质结合蛋白都表现出独特的组织分布模式。由过氧化物酶体增殖物激活受体和CCAAT/增强子结合蛋白共同调控的转录控制，使得细胞和组织特异性表达模式多种多样。在某些细胞中，脂肪酸会增加脂质结合蛋白基因的表达。脂肪酸或其代谢产物是转录因子过氧化物酶体增殖物激活受体家族的激活剂。因此，随着饮食中脂质浓度的增加，脂质结合蛋白的表达也会相应增加。X射线晶体学研究表明，脂质结合蛋白折叠成β桶状结构，形成一个大的内部充满水的腔。脂肪酸配体结合在腔内，仅占据约三分之一的可及体积。结合的脂肪酸通过控制配体亲和力和选择性的焓力和熵力的组合得以稳定。细胞质脂质结合蛋白是疏水配体的细胞内受体，将它们输送到合适的位点用作代谢燃料和调节剂。
