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Molecular dynamics study of the interaction between fatty acid binding proteins with palmitate mini-micelles

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Abstract

The fatty acid binding proteins (FAPBs) function as intracellular carriers of fatty acid (FA) and related compounds. During the digestion of lipids, the local concentration of FA exceeds their critical micellar concentration; the excess ratio of FA/FABP can be as high as ~1,000/1, consequently building micelles. Considering that the micelle formation is a rapid process, the FABP must be able to remove the mini-micelle. In this study, we describe the results of molecular dynamics simulations of liver basic FABP (Lb-FABP), carried out in the presence of ~20 mM palmitate ions, all in the presence of explicit water and at ionic strength of ~100 mM, approximating physiological conditions. The Lb-FABP appears to react, along with a free FA, with mini-micelle creating a stable complex (on the time scale of the simulations), which is attached to the anti-portal domain of the protein. The complex may be formed by the stepwise addition of free FA or through the interaction of a pre-formed mini-micelle with the free protein. The driving force of the mini-micelle-FABP complex is a combination of electrostatic attraction between the negative carboxylates of the mini-micelle with the positive charge of the N terminal amine residues and Lennard-Jones FA–protein interactions. The preferred tendency of the mini-micelle to react with the anti-portal domain retains the α-helixes of the portal region free for its electrostatic interaction with the membrane, ensuring a rapid unloading of the cargo on the membrane.

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References

  1. Mansbach CM, Dowell RF (1992) Uptake and metabolism of circulating fatty acids by rat intestine. Am J Physiol 263:G927–G933

    PubMed  CAS  Google Scholar 

  2. Bass NM, Manning JA, Ockner RK et al (1985) Regulation of the biosynthesis of two distinct fatty acid-binding proteins in rat liver and intestine. Influences of sex difference and of clofibrate. J Biol Chem 260:1432–1436

    PubMed  CAS  Google Scholar 

  3. Haunerland NH, Spener F (2004) Fatty acid-binding proteins—insights from genetic manipulations. Prog Lipid Res 43:328–349. doi:10.1016/j.plipres.2004.05.001

    Article  PubMed  CAS  Google Scholar 

  4. Richieri GV, Ogata RT, Zimmerman AW et al (2000) Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Biochemistry 39:7197–7204. doi:10.1021/bi000314z

    Article  PubMed  CAS  Google Scholar 

  5. Corsico B, Liou HL, Storch J (2004) The alpha-helical domain of liver fatty acid binding protein is responsible for the diffusion-mediated transfer of fatty acids to phospholipid membranes. Biochemistry 43:3600–3607. doi:10.1021/bi0357356

    Article  PubMed  CAS  Google Scholar 

  6. He Y, Yang X, Wang H et al (2007) Solution-state molecular structure of apo and oleate-liganded liver fatty acid-binding protein. Biochemistry 46:12543–12556. doi:10.1021/bi701092r

    Article  PubMed  CAS  Google Scholar 

  7. Likic VA, Prendergast FG (1999) Structure and dynamics of the fatty acid binding cavity in apo rat intestinal fatty acid binding protein. Protein Sci 8:1649–1657

    Article  PubMed  CAS  Google Scholar 

  8. Ory J, Kane CD, Simpson MA et al (1997) Biochemical and crystallographic analyses of a portal mutant of the adipocyte lipid-binding protein. J Biol Chem 272:9793–9801. doi:10.1074/jbc.272.15.9793

    Article  PubMed  CAS  Google Scholar 

  9. Sacchettini JC, Gordon JI, Banaszak LJ (1989) Crystal-structure of rat intestinal fatty-acid-binding protein—refinement and analysis of the Escherichia coli-derived protein with bound palmitate. J Mol Biol 208:327–339. doi:10.1016/0022-2836(89)90392-6

    Article  PubMed  CAS  Google Scholar 

  10. Wu F, Corsico B, Flach CR et al (2001) Deletion of the helical motif in the intestinal fatty acid-binding protein reduces its interactions with membrane monolayers: Brewster angle microscopy, IR reflection–absorption spectroscopy, and surface pressure studies. Biochemistry 40:1976–1983. doi:10.1021/bi002252i

    Article  PubMed  CAS  Google Scholar 

  11. Bakowies D, van Gunsteren WF (2002) Simulations of apo and holo-fatty acid binding protein: structure and dynamics of protein, ligand and internal water. J Mol Biol 315:713–736. doi:10.1006/jmbi.2001.5202

    Article  PubMed  CAS  Google Scholar 

  12. Likic VA, Juranic N, Macura S et al (2000) A “structural” water molecule in the family of fatty acid binding proteins. Protein Sci 9:497–504

    PubMed  CAS  Google Scholar 

  13. Likic VA, Prendergast FG (2001) Dynamics of internal water in fatty acid binding protein: computer simulations and comparison with experiments. Proteins—Struct Funct Genet 43:65–72. doi:10.1002/1097-0134(20010401)43:1<65::AID-PROT1018>3.0.CO;2-F

    Article  PubMed  CAS  Google Scholar 

  14. Tsfadia Y, Friedman R, Kadmon J et al (2007) Molecular dynamics simulations of palmitate entry into the hydrophobic pocket of the fatty acid binding protein. FEBS Lett 581:1243–1247. doi:10.1016/j.febslet.2007.02.033

    Article  PubMed  CAS  Google Scholar 

  15. Friedman R, Nachliel E, Gutman M (2005) Molecular dynamics simulations of the adipocyte lipid binding protein reveal a novel entry site for the ligand. Biochemistry 44:4275–4283. doi:10.1021/bi048236t

    Article  PubMed  CAS  Google Scholar 

  16. Mihajlovic M, Lazaridis T (2007) Modeling fatty acid delivery from intestinal fatty acid binding protein to a membrane. Protein Sci 16:2042–2055. doi:10.1110/ps.072875307

    Article  PubMed  CAS  Google Scholar 

  17. Berendsen HJC, Vanderspoel D, Vandrunen R (1995) Gromacs—a message-passing parallel molecular-dynamics implementation. Comput Phys Commun 91:43–56. doi:10.1016/0010-4655(95)00042-E

    Article  CAS  Google Scholar 

  18. Lindahl E, Hess B, van der Spoel D (2001) Gromacs 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317

    CAS  Google Scholar 

  19. Van der Spoel D, Lindahl E, Hess B et al (2005) GROMACS:fast, flexible, and free. J Comput Chem 26:1701–1718. doi:10.1002/jcc.20291

    Article  CAS  Google Scholar 

  20. Oostenbrink C, Villa A, Mark AE et al (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 25:1656–1676. doi:10.1002/jcc.20090

    Article  PubMed  CAS  Google Scholar 

  21. Nichesola D, Perduca M, Capaldi S et al (2004) Crystal structure of chicken liver basic fatty acid-binding protein complexed with cholic acid. Biochemistry 43:14072–14079

    Article  PubMed  CAS  Google Scholar 

  22. Di Pietro SM, Corsico B, Perduca M et al (2003) Structural and biochemical characterization of toad liver fatty acid-binding protein. Biochemistry 42(27):8192–8203. doi:10.1021/bi034213n

    Article  PubMed  CAS  Google Scholar 

  23. Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28:235–242. doi:10.1093/nar/28.1.235

    Article  PubMed  CAS  Google Scholar 

  24. Mehrotra KN, Upadhyaya SK (1989) Ultrasonic measurements and other allied parameters of praseodymium and neodymium palmitates in mixed organic solvents. Colloid Polym Sci 267:741–747. doi:10.1007/BF01524378

    Article  CAS  Google Scholar 

  25. Berendsen HJC, Postma JPM, van Gunsteren WF et al (1969) Interaction models for water in relation to protein hydration. Nature 224:175–177. doi:10.1038/224175a0

    Article  Google Scholar 

  26. Hess B, Bekker H, Berendsen HJC et al (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18:1463–1472. doi:10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H

    Article  CAS  Google Scholar 

  27. Miyamoto S, Kollman PA (1992) Settle: an analytical version of the shake and rattle algorithms for rigid water models. J Comput Chem 13:952–962. doi:10.1002/jcc.540130805

    Article  CAS  Google Scholar 

  28. Berendsen HJC, Postma JPM, DiNola A et al (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690. doi:10.1063/1.448118

    Article  CAS  Google Scholar 

  29. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N-log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092. doi:10.1063/1.464397

    Article  CAS  Google Scholar 

  30. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14:33–38. doi:10.1016/0263-7855(96)00018-5

    Article  PubMed  CAS  Google Scholar 

  31. Falomir-Lockhart LJ, Laborde L, Kahn PC et al (2006) Protein–membrane interaction and fatty acid transfer from intestinal fatty acid-binding protein to membranes: Support for a multistep process. J Biol Chem 281:13979–13989. doi:10.1074/jbc.M511943200

    Article  PubMed  CAS  Google Scholar 

  32. Corsico B, Franchini GR, Hsu KT et al (2005) Fatty acid transfer from intestinal fatty acid binding protein to membranes: electrostatic and hydrophobic interactions. J Lipid Res 46:1765–1772. doi:10.1194/jlr.M500140-JLR200

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel

    Lihie Ben-Avraham Levin, Esther Nachliel, Menachem Gutman & Yossi Tsfadia

Authors
  1. Lihie Ben-Avraham Levin
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  2. Esther Nachliel
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  3. Menachem Gutman
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  4. Yossi Tsfadia
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Correspondence to Yossi Tsfadia.

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Levin, L.BA., Nachliel, E., Gutman, M. et al. Molecular dynamics study of the interaction between fatty acid binding proteins with palmitate mini-micelles. Mol Cell Biochem 326, 29–33 (2009). https://doi.org/10.1007/s11010-008-0010-4

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  • DOI: https://doi.org/10.1007/s11010-008-0010-4

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