Abstract
Lipid-binding, -transfer or -exchange proteins arepresent in intra- and extracellular fluids of all orgnisms. They play a role in the transport or targeting of lipids in the cell or in the plasma, but may also interact directly or indirectly by modulation of various cellular processes. The structure of these families of lipid-binding proteins, albumin, lipocalin and fatty acid-binding protein (FABP) families, has been established. FABP have similar molecular masses (14-15kDa) and amino acid compositions, exhibit some sequences similarity (38-70%), and form a family with other hydrophobic ligandbinding proteins such as celluar retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP) and intestinal bile acid-binding protein (I-BABP/I-15P/ILBP). At least, 7 types of FABP, liver (L), intestine (I), heart (H), brain (B), myelin (mP2), adipocyte (aP2) or skin type (E/C) FABP, have been isolated from various sources. The large similarity of H-HABP, aP2, mP2 and E/C-FABP (60-70%) is reflected in the similar amino acids on essential positions for fatty acid binding. Interestingly, these FABPs and CRBP I and II contain a protein tyrosine kinase recognition sequence before Tyr 19. The physiological relevance of tyrosine phosphorylation of FABP remains unclear. Furthermore, recently, a significant degree of primary sequence similarity was noted between a domain of an ion channel, the Nmethyl-D-aspartate receptor and the members of the FABP family, while the significance of FABP-like domain for ion channel regulation remains unknown.
X-ray diffraction analysis of FABP family proteins revealed that they show a structure of two short α-heliceslocated near N terminus and fbllowed by 10 anti-parallel β-strands. The β-strands are organized into two nearly orthogonal β-sheets giving the protein the overall appearance of a “clam shell”. To date, the genes for nine members of the FABP family have been identified. The overall organization of the genes is identical, four exons and three introns. The exon/intron boundaries are similar in all genes but the length of the intron sequences varies markedly.
Although FABP has been thought to be involved in the intracellular transport and metabolism of long-chain fatty acids or other hydrophorbic ligands, their physiological roles in cells are not precisely understood. Intracellular fatty acids are important molecules for energy delivery and for synthesis of membrane lipid mediators such as eicosanoids. Apart from their functioning as metabolic substrates and constituents of complex lipids, long-chain fatty acids are being recognized as elements of several cell-to-cell signal transduction pathways. Therefore, it would be interesting to examine mechanisms of the action of FABP involved in these cellular signal transduction.
