Ligand Specificity of Brain Lipid-binding Protein*
- From the ‡ Howard Hughes Medical Institute, Laboratory of Molecular Biology and the
- § Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021-6399
- ∥ To whom correspondence should be addressed: Howard Hughes Medical Institute, Laboratory of Molecular Biology, The Rockefeller University 1230 York Ave., New York, NY 10021-6399 . Tel.: 212-327-7956; Fax: 212-327-7878.
Abstract
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 ~ 0.44 μM) and arachidonic acid (Kd ~ 0.25 μM) 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 ~ 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.
Footnotes
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↵¶ Howard Hughes Medical Institute predoctoral fellow.
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↵* This work was supported by grants from the Howard Hughes Medical Institute (to L. Z. X. and N. H.) and by National Institutes of Health Grant NS 30532 (to N. H.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- BLBP
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brain lipid-binding protein
- FABP
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fatty acid-binding protein
- CRABP
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cellular retinoic acid-binding protein
- ALBP
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adipocyte lipid-binding protein
- DHA
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docosahexaenoic acid
- OA
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oleic acid
- PA
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palmitic acid
- AA
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arachidonic acid
- PCR
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polymerase chain reaction
- LCPUFA
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long chain polyunsaturated fatty acid
- M-FABP
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muscle FABP.
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↵2 MODELLER is available by anonymous ftp from guitar.rockefeller.edu and also as part of QUANTA and Insight II (MSI, San Diego, CA; E-mail: blp{at}MSI.com
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- Received April 19, 1996.
- Revision received July 10, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
