Molecular and Cellular Biochemistry

, Volume 192, Issue 1–2, pp 9–16 | Cite as

The liver fatty acid binding protein - comparison of cavity properties of intracellular lipid-binding proteins

  • James Thompson
  • Jeramia Ory
  • Amy Reese-Wagoner
  • Leonard Banaszak

Abstract

The crystal and solution structures of all of the intracellular lipid binding proteins (iLBPs) reveal a common β-barrel framework with only small local perturbations. All existing evidence points to the binding cavity and a poorly delimited ‘portal’ region as defining the function of each family member. The importance of local structure within the cavity appears to be its influence on binding affinity and specificity for the lipid. The portal region appears to be involved in the regulation of ligand exchange. Within the iLBP family, liver fatty acid binding protein or LFABP, has the unique property of binding two fatty acids within its internalized binding cavity rather than the commonly observed stoichiometry of one. Furthermore, LFABP will bind hydrophobic molecules larger than the ligands which will associate with other iLBPs. The crystal structure of LFABP contains two bound oleate molecules and provides the explanation for its unusual stoichiometry. One of the bound fatty acids is completely internalized and has its carboxylate interacting with an arginine and two serines. The second oleate represents an entirely new binding mode with the carboxylate on the surface of LFABP. The two oleates also interact with each other. Because of this interaction and its inner location, it appears the first oleate must be present before the second more external molecule is bound.

lipid binding proteins fatty acid binding protein intracellular lipids and proteins 

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References

  1. 1.
    Thompson J, Winter N, Terwey D, Bratt J, Banaszak L: The crystal structure of the liver fatty acid binding protein. A complex with two bound oleates. J Biol Chem 272: 7140–7150, 1997Google Scholar
  2. 2.
    Cowan SW, Newcomer ME, Jones AT: Crystallographic studies on a family of cellular lipophilic transport proteins-refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol. J Mol Biol 230: 1225–1246, 1993Google Scholar
  3. 3.
    LaLonde JM, Levenson M, Roe JJ, Bernlohr DA, Banaszak L: Adipocyte lipid-binding protein complexed with arachidonic acid. Titration calorimetry and x-ray crystallographic studies. J Biol Chem 269: 25339–25347, 1994Google Scholar
  4. 4.
    Scapin G, Gordon R, Sacchettini JC: Refinement of the structure of recombinant rat intestinal fatty acid-binding apoprotein at 1.2 Å resolution. J Biol Chem 267: 4253–4269, 1992Google Scholar
  5. 5.
    Young ACM, Scapin G, Kromminga A, Patel SB, Veerkamp JH, Sacchettini JC: Structural studies on human muscle fatty acid binding protein at 1.4 Å resolution: Binding interactions with three C18 fatty acids. Structure 2: 523–534, 1994Google Scholar
  6. 6.
    Haunerland NH, Jacobson BL, Wesenberg G, Rayment I, Holden HM: Three-dimensional structure of the muscle fatty-acid-binding protein isolated from the desert locust Schistocerca gregaria. Biochemistry 33: 12378–12385, 1994Google Scholar
  7. 7.
    Benning MM, Smith AF, Wells MA, Holden HM: Crystallization, structure determination and least-squares refinement to 1.75–Angstrom resolution of the fattyacid binding protein isolated from Manduca Sexta L. J Mol Biol 228: 208–219, 1992Google Scholar
  8. 8.
    Winter NS, Bratt JM, Banaszak L: Crystal structures of holo and apo-cellular retinol-binding protein II. J Mol Biol 230: 1247–1259, 1993Google Scholar
  9. 9.
    Kleywegt GJ, Bergfors T, Senn H, Le Motte P, Gsell B, Shudo K, Jones AT: Crystal structures of cellular retinoic acid binding proteins I and II in complex with all-trans-retinoic acid and a synthetic retinoid. Structure 2: 1241–1258, 1994Google Scholar
  10. 10.
    Bernlohr DA, Simpson MA, Hertzel AV, Banaszak L: Intracellular lipid-binding proteins and their genes. Annu Rev Nutr 17: 277–303, 1997Google Scholar
  11. 11.
    Banaszak L, Winter N, Xu Z, Bernlohr DA, Cowan S, Jones TA: Lipid binding proteins: A family of fatty acid and retinoid binding proteins. Advan Protein Chem 45: 89–151, 1994Google Scholar
  12. 12.
    Glatz, JFC, van der Vusse GJ: Cellular fatty acid-binding proteins: Their function and physiological significance. Prog Lipid Res 35: 242–282, 1996Google Scholar
  13. 13.
    Cistola DP, Sacchettini J, Banaszak L, Walsh M, Gordon J: Fatty acid interactions with rat intestinal and liver fatty acid-binding proteins expressed in Escherichia coli. J Biol Chem 264: 2700–2710, 1989Google Scholar
  14. 14.
    Thumser AE, Wilton DC: The binding of natural and fluorescent lysophospholipids to wild-type and mutant rat liver fatty acid-binding protein and albumin. Biochem J 307: 305–311, 1995Google Scholar
  15. 15.
    Stewart JM, Slysz GW, Pritting MA, Muller-Eberhard U: Ferriheme and ferroheme are isosteric inhibitors of fatty acid binding to rat liver fatty acid binding protein. Biochem Cell Biol 74: 249–255, 1996Google Scholar
  16. 16.
    Rolf B, Oudenampsen-Kruger E, Borchers T, Faergeman NJ, Knudsen J, Lezius A, Spener F: Analysis of the ligand binding properties of recombinant bovine liver type fatty acid binding protein. Biochim Biophys Acta 1259: 245–253, 1995Google Scholar
  17. 17.
    Miller KR, Cistola DP: Titration calorimetry as a binding assay for lipid-binding proteins. Mol Cell Biochem 123: 29–37, 1993Google Scholar
  18. 18.
    Richieri GV, Ogata RT, Kleinfeld AM: Equilibrium constants for the binding of, fatty acids with fatty-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB. J Biol Chem 269: 23918–23930, 1994Google Scholar
  19. 19.
    Borchers T, Spener F: Involvement of arginine in the binding of heme and fatty acids to fatty acid-binding protein from bovine liver. Mol Cell Biochem 123: 23–27, 1993Google Scholar
  20. 20.
    Thumser AE, Evans C, Worrall AF, Wilton DC; Effect on ligand binding of arginine mutations in recombinant rat liver fatty acid-binding protein. Biochem J 297: 103–107, 1994Google Scholar
  21. 21.
    Thumser AE, Voysey J, Wilton DC: Mutations of recombinant rat liver fatty acid-binding protein at residues 102 and 122 alter its structural integrity and affinity for physiological ligands. Biochem J 314: 943–949, 1996Google Scholar
  22. 22.
    Xu Z, Bernlohr DA, Banaszak L: The adipocyte lipid-binding protein at 1.6 Å. Crystal structures of the apoprotein and with bound saturated and unsaturated fatty acids. J Biol Chem 268: 7874–7884, 1993Google Scholar
  23. 23.
    Sacchettini JC, Hauft SM, Van Camp SL, Cistola DP, Gordon JI: Developmental and structural studies of an intracellular lipid binding protein expressed in the ileal epithelium. J Biol Chem 265: 19199–19207, 1990Google Scholar
  24. 24.
    Sacchettini JC, Gordon R, Banaszak U: Crystal structure of rat intestinal fattyacid-binding protein. Refinement and analysis of the Escherichia coli-derived protein with bound palmitate. J Mol Biol 208: 327–339, 1989Google Scholar
  25. 25.
    Prinden CFM, Veerkamp JH: Fatty acid binding and conformational stability of mutants of human muscle fatty acid-binding protein. Biochem J 314: 253–260, 1996Google Scholar
  26. 26.
    Jakoby MG, Miler KR, Toner JJ, Bauman A, Cheng L, Li E, Cistola DP: Ligand-protein electrostatic interactions govern the specificity of retinol-and fatty acid-binding proteins. Biochemistry 32: 872–878, 1993Google Scholar
  27. 27.
    Cheng L, Qian S, Rothschild C, Avignon A, Lefkowith J, Gordon J, Li E: Alteration of the binding specificity of cellular retinol-binding protein II by site-directed mutagenesis. J Biol Chem 267: 24404–24412, 1992Google Scholar
  28. 28.
    Richieri GV, Low PJ, Ogata RT, Kleinfeld AM: Mutants of rat intestinal fatty acid-binding protein illustrate the critical role played by enthalpy-entropy compensation in ligand binding. J Biol Chem 272: 16737–16740, 1997Google Scholar
  29. 29.
    Herr FM, Matarese V, Bernlohr DA, Storch J: Surface lysine residues modulate the collisional transfer of fatty acid from adiptocyte fatty acid binding protein to membranes. Biochemistry 34: 11840–11845, 1995Google Scholar
  30. 30.
    Ory J, Kane CD, Simpson MA, Banaszak U, Bernlohr DA: Biochemical and crystal lographic analyses of a portal mutant of the adipocyte lipid-binding protein. J Biol Chem 272: 9793–9801, 1997Google Scholar
  31. 31.
    Herr FM, Aronson J, Storch J: Role of portal region lysine residues in electrostatic interactions between heart fatty acid binding protein and phospholipid membranes. Biochemistry 35: 1296–1303, 1996Google Scholar
  32. 32.
    Cistola DP, Kim K, Rogl H, Frieden C: Fatty acid interactions with a helix-less variant of intestinal fatty acid-binding protein. Biochemistry 35: 7559–7565, 1996Google Scholar
  33. 33.
    Honma Y, Niimi M, Uchiumi T, Takahashi Y, Odani S: Evidence for conformational change of fatty acid-binding protein accompanying binding of hydrophobic ligands. Biochem J 116: 1025–1029, 1994Google Scholar
  34. 34.
    Rizo J, Liu A, Gierasch LM: 1H and 15N resonance assignments and secondary structure of cellular retinoic acid-binding protein with and without bound ligand. J Biomol NMR 4: 741–760, 1994Google Scholar
  35. 35.
    Jamison RS, Newcomer ME, Ong DE: Cellular retinoic acid binding proteins: Limited proteolysis reveals a conformational change upon ligand binding. Biochemistry 33: 2873–2879, 1994Google Scholar
  36. 36.
    Ropson IJ, Gordon JI, Frieden C: Folding of a predominately betastructure protein: Rat intestinal fatty acid binding protein. Biochemistry 29: 9591–9599, 1990Google Scholar
  37. 37.
    Thompson JR, Bratt JM, Banaszak U: Crystal structure of cellular retinoic acid binding protein I shows increased access to the binding cavity due to formation of an intermolecular β-sheet. J Mol Biol 252: 433–446, 1995Google Scholar
  38. 38.
    Ji X, Chen X, Tordova M, Gilliland GL, Wang L, Li Y, Yan Honggao: Crystal structure of apo-cellular retinoic acid binding protein type II suggests a mechanism of ligand entry. ACA Annual Meeting Abstracts, St. Louis, MO, 1997Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • James Thompson
    • 1
  • Jeramia Ory
    • 1
  • Amy Reese-Wagoner
    • 1
  • Leonard Banaszak
    • 1
  1. 1.Department of BiochemistryUniversity of MinnesotaMinneapolisUSA

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