Structural and functional analysis of fatty acid-binding proteins

The mammalian FA-binding proteins (FABPs) bind long-chain FA with high affinity. The large number of FABP types is suggestive of distinct functions in specific tissues. Multiple experimental approaches have shown that individual FABPs possess both unique and overlapping functions, some of which are based on specific elements in the protein structure. Although FA binding affinities for all FABPs tend to correlate directly with FA hydrophobicity, structure-function studies indicate that subtle three-dimensional changes that occur upon ligand binding may promote specific protein-protein or protein-membrane interactions that ultimately determine the function of each FABP. The conformational changes are focused in the FABP helical/portal domain, a region that was identified by in vitro studies to be vital for the FA transport properties of the FABPs. Thus, the FABPs modulate intracellular lipid homeostasis by regulating FA transport in the nuclear and extra-nuclear compartments of the cell; in so doing, they also impact systemic energy homeostasis. The mammalian FA-binding proteins (FABPs) bind long-chain FA with high affinity. The large number of FABP types is suggestive of distinct functions in specific tissues. Multiple experimental approaches have shown that individual FABPs possess both unique and overlapping functions, some of which are based on specific elements in the protein structure. Although FA binding affinities for all FABPs tend to correlate directly with FA hydrophobicity, structure-function studies indicate that subtle three-dimensional changes that occur upon ligand binding may promote specific protein-protein or protein-membrane interactions that ultimately determine the function of each FABP. The conformational changes are focused in the FABP helical/portal domain, a region that was identified by in vitro studies to be vital for the FA transport properties of the FABPs. Thus, the FABPs modulate intracellular lipid homeostasis by regulating FA transport in the nuclear and extra-nuclear compartments of the cell; in so doing, they also impact systemic energy homeostasis. The family of cytoplasmic FA-binding proteins (FABPs) evolved by successive gene duplications generating a large number of tissue specific homologs. The mammalian family includes nine FABPs, the cellular retinoid binding proteins, and a newly discovered retinal form whose ligand binding properties are not known (1Liu R.Z. Li X. Godbout R. A novel fatty acid-binding protein (FABP) gene resulting from tandem gene duplication in mammals: transcription in rat retina and testis.Genomics. 2008; 92: 436-445Crossref PubMed Scopus (98) Google Scholar, 2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar). Tissues with high rates of FA uptake and lipid metabolism have high expression of one or more FABPs. The large diversity of FABPs, which contrasts sharply with other lipid-binding proteins, has long been suggestive of functional specialization. It is now clear that there are both unique and overlapping functions for specific FABPs (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar). In this brief review, we will focus on those functions of different FABPs where the structural elements that may underlie these functions are beginning to be understood. Despite modest amino acid sequence homologies, the FABPs exhibit very similar tertiary structures. Their 10 anti-parallel β-strands are organized into 2 nearly orthogonal β-sheets that form a slightly elliptical β-barrel, with 2 8-10 residue helixes linking the first 2 β-strands (3Banaszak L. Winter N. Xu Z.H. Bernlohr D.A. Cowan S. Jones T.A. Lipid-binding proteins- a family of fatty-acid and retinoid transport proteins.Adv. Protein Chem. 1994; 45: 89-151Crossref PubMed Google Scholar, 4Zhang F. Lucke C. Baier L.J. Sacchettini J.C. Hamilton J.A. Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T) that is associated with altered lipid metabolism.Biochemistry. 2003; 42: 7339-7347Crossref PubMed Scopus (27) Google Scholar) (Fig. 1A). The helix-turn-helix motif, from which the ligand-binding cavity extends, is thought to act as a portal for FA access and egress (3Banaszak L. Winter N. Xu Z.H. Bernlohr D.A. Cowan S. Jones T.A. Lipid-binding proteins- a family of fatty-acid and retinoid transport proteins.Adv. Protein Chem. 1994; 45: 89-151Crossref PubMed Google Scholar), with the α-II helix forming long-range interactions with the α-II turn between β-strands C and D. The FABP binding cavity is considerably larger than its ligand (3Banaszak L. Winter N. Xu Z.H. Bernlohr D.A. Cowan S. Jones T.A. Lipid-binding proteins- a family of fatty-acid and retinoid transport proteins.Adv. Protein Chem. 1994; 45: 89-151Crossref PubMed Google Scholar). All the FABPs bind FA with its carboxylate group oriented inside the cavity, interacting with interior Arg residues and other side chains (5Richieri G.V. Ogata R.T. Kleinfeld A.M. Fatty acid interactions with native and mutant fatty acid binding proteins.Mol. Cell. Biochem. 1999; 192: 77-85Crossref PubMed Google Scholar). Solution structures of apo FABPs reveal specific regions of disorder in the portal domain, compared with holo-FABP structures (5Richieri G.V. Ogata R.T. Kleinfeld A.M. Fatty acid interactions with native and mutant fatty acid binding proteins.Mol. Cell. Biochem. 1999; 192: 77-85Crossref PubMed Google Scholar, 6He Y. Yang X. Wang H. Estephan R. Francis F. Kodukula S. Storch J. Stark R.E. Solution-state molecular structure of apo and oleate-liganded liver fatty acid-binding protein.Biochemistry. 2007; 46: 12543-12556Crossref PubMed Scopus (60) Google Scholar). Thus, it is likely that a conformational change in the portal region occurs during FA binding or release. FABP-membrane interactions or protein-protein interactions may catalyze this conformational change. Despite its similar fold, the liver FABP (LFABP) alone can bind an additional FA, as well as other larger hydrophobic molecules (6He Y. Yang X. Wang H. Estephan R. Francis F. Kodukula S. Storch J. Stark R.E. Solution-state molecular structure of apo and oleate-liganded liver fatty acid-binding protein.Biochemistry. 2007; 46: 12543-12556Crossref PubMed Scopus (60) Google Scholar). All FABPs bind both saturated and unsaturated long-chain (≥ 14C) FA. Binding affinity values obtained using the ADIFAB method indicate dissociation constant (Kd) values in the nanomolar range. None of the FABPs show a distinct specificity for a particular FA, and the binding affinities for all FABPs correlate directly with FA hydrophobicity (7Richieri G.V. Ogata R.T. Zimmerman A.W. Veerkamp J.H. Kleinfeld A.M. Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions.Biochemistry. 2000; 39: 7197-7204Crossref PubMed Scopus (140) Google Scholar). Thus, a paradox is apparent: why are there multiple FABPs if their ligand binding capacities and specificities, with LFABP as a possible exception, are roughly the same? We hypothesize that unique functional properties of individual FABPs may be dictated in large part by structural characteristics of the proteins’ surfaces rather than strictly by ligand binding specificity. In vitro studies have shown that different FABPs transfer FA to membranes by two different transfer mechanisms. LFABP transfers ligand to and from membranes by aqueous phase diffusion (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). In marked contrast, a larger number of the FABPs, including the adipocyte, keratinocyte, intestinal, brain, myelin, and heart/muscle types, transfer their FA by directly interacting with a membrane (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). Evaluation of the structural elements underlying the two in vitro transfer mechanisms has identified the FABP helix-turn-helix/portal domain as the major determinant of its FA transfer mechanism (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar, 8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). Protein-membrane interactions are supported by the net positive surface electrostatic potential across the portal region of collisional FABPs (9LiCata V.J. Bernlohr D.A. Surface properties of adipocyte lipid-binding protein: response to lipid binding, and comparison with homologous proteins.Proteins. 1998; 33: 577-589Crossref PubMed Scopus (40) Google Scholar) and the amphipathic character of their α-I helices in particular (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar, 9LiCata V.J. Bernlohr D.A. Surface properties of adipocyte lipid-binding protein: response to lipid binding, and comparison with homologous proteins.Proteins. 1998; 33: 577-589Crossref PubMed Scopus (40) Google Scholar) (Fig. 1B). As the physiological roles of individual FABPs have begun to emerge in recent years, it is becoming possible to link their functional properties with an understanding of the structural characteristics that underlie their mechanisms of action. As with the in vitro FA transfer studies, the available data point to the helix-turn-helix/portal region of the FABPs as a critical domain determining many of the functions of this diverse family of proteins. In the following sections, the structure-function relationships that appear to define specific functions of different FA-binding FABPs will be discussed. Adipocyte FABP (AFABP) and the keratinocyte FABP (KFABP) are both expressed in adipocytes and macrophages. AFABP is in far greater abundance in fat cells, while equivalent levels of AFABP and KFABPs are found in macrophages. Described below (and in Fig. 2) are similarities in the regulation and function of AFABP and KFABPs; individual properties of KFABP are described thereafter. Both AFABP and KFABPs transfer FA to membranes via collisional interaction (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). Basic residues in the helix-turn-helix domain of AFABP, in particular K21 and K31, were identified as vital for the collisional transfer process (10Liou H.L. Storch J. Role of surface lysine residues of adipocyte fatty acid-binding protein in fatty acid transfer to phospholipid vesicles.Biochemistry. 2001; 40: 6475-6485Crossref PubMed Scopus (31) Google Scholar). AFABP interacts with hormone-sensitive lipase (HSL) and K21 is required for interaction (11Smith A.J. Thompson B.R. Sanders M.A. Bernlohr D.A. Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase: regulation by fatty acids and phosphorylation.J. Biol. Chem. 2007; 282: 32424-32432Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). HSL phosphorylation, oleic acid binding by AFABP, and charged residues in AFABP’s α-helical domain (D17, D18, and R30) are also necessary for HSL interaction (12Smith A.J. Sanders M.A. Juhlmann B.E. Hertzel A.V. Bernlohr D.A. Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid binding protein: identification of the charge quartet on the AFABP/ap2 helix-turn-helix domain.J. Biol. Chem. 2008; (Epub ahead of print.)Abstract Full Text Full Text PDF Scopus (32) Google Scholar). These four portal residues are conserved in which also interacts with not in intestinal FABPs and which not (12Smith A.J. Sanders M.A. Juhlmann B.E. Hertzel A.V. Bernlohr D.A. Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid binding protein: identification of the charge quartet on the AFABP/ap2 helix-turn-helix domain.J. Biol. Chem. 2008; (Epub ahead of print.)Abstract Full Text Full Text PDF Scopus (32) Google Scholar). studies show that on AFABP an with on and K21 on AFABP interacts with on HSL (12Smith A.J. Sanders M.A. Juhlmann B.E. Hertzel A.V. Bernlohr D.A. Mapping of the hormone-sensitive lipase binding site on the adipocyte fatty acid binding protein: identification of the charge quartet on the AFABP/ap2 helix-turn-helix domain.J. Biol. Chem. 2008; (Epub ahead of print.)Abstract Full Text Full Text PDF Scopus (32) Google Scholar). The of AFABP, and have to their cellular and systemic the individual gene modest for both A and KFABPs were found to be and (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar, Fatty acid-binding in and potential as Rev. 2008; PubMed Scopus Google Scholar). a comparison of lipid from and that tissue and from levels of the H. of a a lipid linking tissue to systemic 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). and the saturated were directly compared by with and and by systemic into the that in liver and to the of from is an and additional studies, to the other major of by will indicate the unique properties of the FABP on an of the binding affinities of FABP types for different FA, including it is not that have an interaction with AFABP (7Richieri G.V. Ogata R.T. Zimmerman A.W. Veerkamp J.H. Kleinfeld A.M. Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions.Biochemistry. 2000; 39: 7197-7204Crossref PubMed Scopus (140) Google Scholar). As FA binding affinities correlate with ligand and have affinities than their and and other were found to have dissociation of that found for (7Richieri G.V. Ogata R.T. Zimmerman A.W. Veerkamp J.H. Kleinfeld A.M. Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions.Biochemistry. 2000; 39: 7197-7204Crossref PubMed Scopus (140) Google Scholar). as specific that not in affinity may in structural on the FABP of and are of lipid metabolism and energy homeostasis. AFABP was shown to the of and KFABP of A and KFABPs to the in specific response to for and and and interactions were The tertiary structures of AFABP to and acid AFABP in which portal residues were K21 on helix and and on these form a nuclear In contrast, AFABP with or that not not show a R.E. N. for of fatty acid-binding protein Biol. 2007; PubMed Scopus Google Scholar). residues and to of turn elements the form a nuclear in the tertiary structure R.E. N. of by 2007; 46: PubMed Scopus Google Scholar). These studies indicate that FABP functional properties are not by FA binding properties as the binding of specific to A or KFABPs subtle conformational changes in their portal for specific functional interactions to It will be of to determine distinct surface structural changes that for its function as an lipid In to adipocytes and KFABP is expressed in brain, and tissue (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar) and to roles in KFABP acid with a of similar to its binding affinity for FA N. of acid on from of two different nuclear 2007; Full Text Full Text PDF PubMed Scopus Google Scholar), and this has for its in by binding to the nuclear it can also promote by binding to and of N. of acid on from of two different nuclear 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). The underlying mechanism of these are to interactions of and with to or or is by the of binding protein with a high to of and a to L. N. of by acid from to 2008; PubMed Scopus Google Scholar). a of it was shown that the in tissue from to and L. N. of by acid from to 2008; PubMed Scopus Google Scholar). KFABP is from other of the FABP family by a large number of and it has been to a in regulating the cellular S. Y. H. in rat fatty acid-binding Biochem. 2000; PubMed Scopus Google Scholar). In and form a link the ligand binding cavity and are in to the FA It has been shown that can be by a lipid in response to and L. Hertzel A.V. D.A. Bernlohr D.A. of fatty acid-binding protein by in vitro and in for a in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), that KFABP functions as an protein by of L. Hertzel A.V. D.A. Bernlohr D.A. of fatty acid-binding protein by in vitro and in for a in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). KFABP has been shown to form a with a protein A.M. interacts with fatty acid binding protein and in structures in 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). In of and KFABP in the protein-protein from the to structures upon of A.M. interacts with fatty acid binding protein and in structures in 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The functional of these and the structural for the interaction are LFABP has been to be in lipid by the and in lipid transport and unique binding and surface characteristics are likely to to its specific functional In to the binding of long-chain FA by other FABPs, LFABP two FA, one in a similar to other FABPs, with the carboxylate interacting with and in the binding cavity, and the with its group interacting with and the protein surface in the portal region (6He Y. Yang X. Wang H. Estephan R. Francis F. Kodukula S. Storch J. Stark R.E. Solution-state molecular structure of apo and oleate-liganded liver fatty acid-binding protein.Biochemistry. 2007; 46: 12543-12556Crossref PubMed Scopus (60) Google Scholar). Binding of the surface ligand is unique to and binding of the FA binding of the H. Y. Kodukula S. Storch J. Stark R.E. and studies of liver fatty acid-binding protein with long-chain fatty PubMed Scopus Google Scholar). The binding affinities of the two FA are similar for saturated fatty the site has affinity for unsaturated FA than the surface site G.V. Ogata R.T. Kleinfeld A.M. for the binding of with proteins from adipocyte, and liver with the Biol. Chem. 1994; Full Text PDF PubMed Google Scholar). LFABP also a of other hydrophobic as and (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). The of these is in part to the larger cavity of LFABP to other FABPs J. J. and L. The liver fatty acid binding protein: comparison of cavity properties of intracellular lipid binding proteins.Mol. Cell. Biochem. 1999; 192: PubMed Google Scholar). LFABP is the FA-binding of the mammalian FABP family to transfer FA to membranes by aqueous with FABPs show that the helix-turn-helix domain of LFABP can a mechanism of FA transfer to the binding of an collisional FABP (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar, 8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). can be in large part to the that of LFABP is LFABP with membranes to a in cells, protein-protein studies have a nuclear for LFABP C. F. Fatty acids and and gene expression via liver fatty acid binding protein: a to the 2001; PubMed Scopus Google Scholar). interactions with have been and by FA was found to be directly with cellular LFABP C. F. Fatty acids and and gene expression via liver fatty acid binding protein: a to the 2001; PubMed Scopus Google Scholar). Thus, it is possible that the regulation of gene expression is a function of the FABP the structural of interaction has not been and the residues identified on A and KFABPs are not conserved in LFABP show both and as with other FABP or with or other FABPs occurs in LFABP unique functions for these proteins. show a in fatty acid which is likely to a in FA changes in gene expression are found H. F. B. liver fatty acid binding and altered liver lipid in the liver fatty acid-binding protein Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, Y. and in liver fatty acid-binding protein PubMed Scopus Google Scholar). while fatty liver on a or following the were from in both H. F. B. liver fatty acid binding and altered liver lipid in the liver fatty acid-binding protein Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, Y. and in liver fatty acid-binding protein PubMed Scopus Google Scholar). The the was high in saturated FA, not a high was Y. and in is with not and J. 2008; PubMed Scopus Google Scholar). may not be to ligand binding LFABP has specificity for binding unsaturated rather than saturated FA. the indicate that LFABP may be in of FA to specific lipid function of LFABP in is by lipid in Y. and in liver fatty acid-binding protein PubMed Scopus Google Scholar) and by studies of where LFABP was shown to be for the of transport from the S. J. B. Storch J. fatty acid-binding protein of transport from intestinal Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar). intestinal both and The clear in ligand binding properties and FA transfer mechanisms are based on structural between the two FABPs. The of the binding cavity of is of the LFABP cavity J. J. and L. The liver fatty acid binding protein: comparison of cavity properties of intracellular lipid binding proteins.Mol. Cell. Biochem. 1999; 192: PubMed Google Scholar) as a of side chains that into the ligand to the specificity of for long-chain FA and not other lipid molecules (6He Y. Yang X. Wang H. Estephan R. Francis F. Kodukula S. Storch J. Stark R.E. Solution-state molecular structure of apo and oleate-liganded liver fatty acid-binding protein.Biochemistry. 2007; 46: 12543-12556Crossref PubMed Scopus (60) Google Scholar). The collisional mechanism of FA transfer between and membranes has been shown by to be in large part by electrostatic interactions between charged in the domain of the protein and of phospholipid residues in the α-II are of particular (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar). and with an greater and to L. The intestinal fatty acid binding protein is not for fat in J. 2000; PubMed Scopus (140) Google Scholar). a in intestinal lipid and that may be of the A in the human gene resulting in an to substitution residue is associated with and in A of intestinal fatty acid binding protein gene and the response to Biochem. 1998; PubMed Scopus (32) Google Scholar), additional for a in energy and the FA with greater affinity than the FA levels (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar, L.J. Sacchettini J.C. J. H. C. substitution in the human intestinal protein is associated with fat and PubMed Scopus Google Scholar). Thus, the FA binding affinity not into lipid from the a more specific for in FA in in the turn between β-strands C and is part of the ligand portal domain, forming long-range interactions with the α-II helix (Fig. 1B). structures of the and that structural occur in the of the with the larger side of likely the of dissociation of FA from the binding the affinity F. Lucke C. Baier L.J. Sacchettini J.C. Hamilton J.A. Solution structure of human intestinal fatty acid binding protein with a naturally-occurring single amino acid substitution (A54T) that is associated with altered lipid metabolism.Biochemistry. 2003; 42: 7339-7347Crossref PubMed Scopus (27) Google Scholar). is this structural and binding in be of the systemic understanding of the potential functions of other FABPs is In vitro FA transfer from the heart/muscle FABP to membranes is with the helical/portal region a determinant of its ligand transfer mechanism (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). functions in the transport and metabolism of FA is clear from the of the which FA uptake into the and FA (2Storch J. Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins.Annu. Rev. Nutr. 2008; 28: 73-95Crossref PubMed Scopus (302) Google Scholar). of with and expression of in their in a for in and Y. N. Li F. Veerkamp J.H. of the protein family are for the Biol. 1994; PubMed Scopus Google Scholar). It has been that the structural for these is the of the expressed in this which the of in vitro and in H.L. by of the 2000; PubMed Scopus Google Scholar). that of may be of their FA and in the are Y. N. H. H. Y. H. Y. in fatty acid-binding protein J. PubMed Scopus Google Scholar), in response to the FA acid was and was found in Y. N. H. H. Y. H. Y. in fatty acid-binding protein J. PubMed Scopus Google Scholar). is found in high in brain, and was to have a greater affinity for than for an specificity or in affinity between and (7Richieri G.V. Ogata R.T. Zimmerman A.W. Veerkamp J.H. Kleinfeld A.M. Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions.Biochemistry. 2000; 39: 7197-7204Crossref PubMed Scopus (140) Google Scholar). As binding properties may not be of FABP It was that the structural of specificity for may be to an interior residue which interacts with the unsaturated in the F. N. Godbout R. F. Sacchettini J.C. structure and of human fatty acid-binding Biol. Chem. 2000; Full Text Full Text PDF PubMed Google Scholar). The protein as is unique in been shown to be an membrane its membrane interaction to some with all collisional transfer FABPs are likely to be and may its function in (8Storch J. Thumser A.E.A. The fatty acid transport function of fatty acid-binding proteins.Biochim. Biophys. Acta. 2000; 1486: 28-44Crossref PubMed Scopus (421) Google Scholar). The FABPs function in intracellular lipid also systemic lipid FABPs possess unique and overlapping functions that are to transport and metabolism of long-chain FA. structure-function studies of A and KFABPs that subtle changes that occur upon ligand binding may promote specific or FABP-membrane interactions that ultimately determine the particular function of the FABP. The conformational changes are focused in the FABP helical/portal domain, a region that was identified by in vitro studies to be for the FA transport properties of specific FABPs.