Gordon J I, Lowe J B
Chem Phys Lipids. 1985 Aug 30;38(1-2):137-58. doi: 10.1016/0009-3084(85)90063-5.
The structures of intestinal and liver fatty acid binding proteins (FABPs) have been determined from an analysis of the nucleotide sequences of cloned cDNAs. The primary translation product of intestinal FABP mRNA contains 132 residues (Mr = 15 124). Liver FABP mRNA encodes a 127 amino acid polypeptide (Mr = 14 273). In vitro co-translational cleavage and translocation assays showed that neither sequence has a cleavable signal peptide or signal peptide equivalent - suggesting that the FABPs do not enter the secretory apparatus but rather are targeted to the cytoplasm. A variety of computational techniques were used to compare the two FABP sequences. The results indicate that liver and intestinal FABP are paralogous homologues. A superfamily of proteins was defined which includes the FABPs, the cellular retinol and retinoic acid binding proteins, the P2 protein of peripheral nerve myelin, and a polypeptide known as 422 whose synthesis is induced during differentiation of 3T3-L1 cells to adipocytes. No sequence homologies were noted between any of these small molecular weight cytosolic proteins and nonspecific lipid transfer protein (sterol carrier protein 2), phosphatidylcholine transfer protein, serum albumin or apolipoprotein AI. The FABPs may have structural features responsible for lipid-protein interactions that are not present in these non-homologous sequences. The distribution of intestinal and liver FABP mRNAs in adult rat tissues and the changes in FABP gene expression which occur during gastrointestinal development support the notion that these proteins are involved in fatty acid uptake, transport and/or compartmentalization. However, differences in tissue distribution and periods of non-coordinate expression during gastrointestinal ontogeny suggest that the two FABPs have distinct functions. The relationship between intestinal and liver FABPs and similar sized cytosolic FABPs isolated from brain, skeletal and cardiac muscle remains unclear. Recombinant DNA techniques combined with comparative sequence analyses offer a useful approach for defining unique as well as general structure-function relationships in this group of fatty acid binding proteins.
通过对克隆的cDNA核苷酸序列进行分析，已确定了肠道和肝脏脂肪酸结合蛋白（FABP）的结构。肠道FABP mRNA的初级翻译产物包含132个残基（Mr = 15124）。肝脏FABP mRNA编码一个127个氨基酸的多肽（Mr = 14273）。体外共翻译切割和转运试验表明，这两个序列都没有可切割的信号肽或等效的信号肽，这表明FABP不会进入分泌装置，而是定位于细胞质。使用了多种计算技术来比较这两个FABP序列。结果表明，肝脏和肠道FABP是旁系同源物。定义了一个蛋白质超家族，其中包括FABP、细胞视黄醇和视黄酸结合蛋白、周围神经髓鞘的P2蛋白，以及一种称为422的多肽，其合成在3T3-L1细胞向脂肪细胞分化过程中被诱导。在这些小分子细胞质蛋白与非特异性脂质转运蛋白（固醇载体蛋白2）、磷脂酰胆碱转运蛋白、血清白蛋白或载脂蛋白AI之间未发现序列同源性。FABP可能具有负责脂质 - 蛋白质相互作用的结构特征，而这些特征在这些非同源序列中不存在。成年大鼠组织中肠道和肝脏FABP mRNA的分布以及胃肠道发育过程中FABP基因表达的变化支持了这些蛋白质参与脂肪酸摄取、运输和/或分隔的观点。然而，胃肠道个体发育过程中组织分布和非协调表达时期的差异表明，这两种FABP具有不同的功能。肠道和肝脏FABP与从脑、骨骼肌和心肌中分离出的大小相似的细胞质FABP之间的关系仍不清楚。重组DNA技术与比较序列分析相结合，为确定这组脂肪酸结合蛋白中独特的以及一般的结构 - 功能关系提供了一种有用的方法。
