Ligand specificity of brain lipid-binding protein

Brain lipid-binding protein (BLBP) is a member of the fatty acid-binding protein (FABP) family. Although BLBP expression in the developing central nervous system is complex, a close correlation between its expression and radial glial differentiation has been observed. Furthermore, antibodies to BLBP can block glial cell differentiation in mixed primary cell cultures. Here we describe the ligand binding properties of BLBP. The binding affinities of BLBP for oleic acid (Kd approximately 0.44 microM) and arachidonic acid (Kd approximately 0.25 microM) are similar to those reported for other FABPs, but BLBP does not bind to palmitic acid or arachidinic acid. These and other experiments establish that BLBP has a strong preference for binding long chain polyunsaturated fatty acids. A probable in vivo ligand for BLBP is docosahexaenoic acid (DHA), since its binding affinity (Kd approximately 10 nM) is the highest yet reported for an FABP/ligand interaction, exceeding even the affinity of retinoic acid for its binding proteins. Furthermore, the requirement of DHA for nervous system development and the coincident expression of BLBP during these developmental stages suggest that the physiologic role of BLBP may involve DHA utilization. Finally, we present a structural model of BLBP/DHA interaction that provides insight into both the structural characteristics important for ligand binding and the effects of specific mutations upon BLBP/ligand interactions.