Crystal structure and thermodynamic analysis of human brain fatty acid-binding protein

Expression of brain fatty acid-binding protein (B-FABP) is spatially and te mporally correlated with neuronal differentiation during brain development. Isothermal titration calorimetry demonstrates that recombinant human B-FAB P clearly exhibits high affinity for the polyunsaturated n-3 fatty acids cy -linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, and for monou nsaturated n-9 oleic acid (K-d from 28 to 53 nM) over polyunsaturated n-6 f atty acids, linoleic acid, and arachidonic acid (K-d from 115 to 206 nhl), B-FABP has low binding affinity for saturated long chain fatty acids. The t hree-dimensional structure of recombinant human B-FABP in complex with olei c acid shows that the oleic acid hydrocarbon tail assumes a "U-shaped" conf ormation, whereas in the complex with docosahexaenoic acid the hydrocarbon tail adopts a helical conformation. A comparison of the three dimensional s tructures and binding properties of human B-FABP with other homologous FABP s, indicates that the binding specificity is in part the result of nonconse rved amino acid Phe(104), which interacts with double bonds present in the lipid; hydrocarbon tail. In this context, analysis of the primary and terti ary structures of human B-FABP provides a rationale for its high affinity a nd specificity for polyunsaturated fatty acids. The expression of B-FABP in glial cells and its high affinity for docosahexaenoic acid, which is known to be an important component of neuronal membranes, points toward a role f or B-FABP in sup plying brain abundant fatty acids to the developing neuron .