Article

You have free access to this content

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: A study using charge-specific chemical modifications

  1. Yongjing Xie1,
  2. Soyoung Min1,
  3. Níal P. Harte1,
  4. Hannah Kirk1,
  5. John E. O'Brien2,
  6. H. Paul Voorheis1,
  7. Catharina Svanborg3,
  8. K. Hun Mok1,3,4,*

Article first published online: 29 SEP 2012

DOI: 10.1002/prot.24141

Issue

Proteins: Structure, Function, and Bioinformatics

Proteins: Structure, Function, and Bioinformatics

Volume 81, Issue 1, pages 1–17, January 2013

Additional Information

How to Cite

Xie, Y., Min, S., Harte, N. P., Kirk, H., O'Brien, J. E., Voorheis, H. P., Svanborg, C. and Hun Mok, K. (2013), Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: A study using charge-specific chemical modifications. Proteins, 81: 1–17. doi: 10.1002/prot.24141

Author Information

  1. 1

    Trinity Biomedical Sciences Institute (TBSI), School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland

  2. 2

    School of Chemistry, Trinity College Dublin, Dublin 2, Ireland

  3. 3

    Department of Microbiology, Immunology and Glycobiology (MIG), Faculty of Medicine, Institute for Laboratory Medicine (ILM), Lund University, Sölvegatan 23, S-223 62 Lund, Sweden

  4. 4

    Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, Ireland

*Trinity Biomedical Sciences Institute (TBSI), School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland

Publication History

  1. Issue published online: 15 DEC 2012
  2. Article first published online: 29 SEP 2012
  3. Accepted manuscript online: 7 JUL 2012 12:56AM EST
  4. Manuscript Accepted: 27 JUN 2012
  5. Manuscript Revised: 15 JUN 2012
  6. Manuscript Received: 5 APR 2012

Funded by

  • Irish Food Institutional Research Measure (FIRM). Grant Number: 08RDTMFRC650
  • Swedish Cancer Foundation
  • American Cancer Society
  • Heart and Lung Foundation and the American Lung Society
  • Swedish Research Council (Vetenskapsrådet). Grant Number: 2007-3688

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (604K)

REFERENCES

  • 1
    Permyakov EA,Berliner LJ. α-Lactalbumin: structure and function. FEBS Lett 2000; 473: 269–274.
  • 2
    Håkansson A,Zhivotovsky B,Orrenius S,Sabharwal H,Svanborg C. Apoptosis induced by a human milk protein. Proc Natl Acad Sci U S A 1995; 92: 8064–8068.
  • 3
    Svensson M,Håkansson A,Mossberg AK,Linse S,Svanborg C. Conversion of α-lactalbumin to a protein inducing apoptosis. Proc Natl Acad Sci U S A 2000; 97: 4221–4226.
  • 4
    Håkansson A,Andréasson J,Zhivotovsky B,Karpman D,Orrenius S,Svanborg C. Multimeric α-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei. Exp Cell Res 1999; 246: 451–460.
  • 5
    Aits S,Gustafsson L,Hallgren O,Brest P,Gustafsson M,Trulsson M,Mossberg AK,Simon HU,Mograbi B,Svanborg C. HAMLET (human α-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. Int J Cancer 2009; 124: 1008–1019.
    Direct Link:
  • 6
    Gustafsson L,Aits S,Önnerfjord P,Trulsson M,Storm P,Svanborg C. Changes in proteasome structure and function caused by HAMLET in tumor cells. PLoS One 2009; 4: e5229.
  • 7
    Rammer P,Groth-Pedersen L,Kirkegaard T,Daugaard M,Rytter A,Szyniarowski P,Høyer-Hansen M,Povlsen LK,Nylandsted J,Larsen JE,Jäättelä M. BAMLET activates a lysosomal cell death program in cancer cells. Mol Cancer Ther 2010; 9: 24–32.
  • 8
    Svanborg C,Ågerstam H,Aronsson A,Bjerkvig R,Düringer C,Fischer W,Gustafsson L,Hallgren O,Leijonhuvud I,Linse S,Mossberg AK,Nilsson H,Pettersson J,Svensson M. HAMLET kills tumor cells by an apoptosis-like mechanism-cellular, molecular, and therapeutic aspects. Adv Cancer Res 2003; 88: 1–29.
  • 9
    Min S,Meehan J,Sullivan LM,Harte NP,Xie Y,Davey GP,Svanborg C,Brodkorb A,Mok KH. Alternatively folded proteins with unexpected beneficial functions. Biochem Soc Trans 2012; 40: 746–751.
  • 10
    Pettersson-Kastberg J,Aits S,Gustafsson L,Mossberg A,Storm P,Trulsson M,Persson F,Mok KH,Svanborg C. Can misfolded proteins be beneficial? The HAMLET case. Ann Med 2009; 41: 162–176.
  • 11
    Mossberg AK,Mok KH,Morozova-Roche LA,Svanborg C. Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes. FEBS J 2010; 277: 4614–4625.
    Direct Link:
  • 12
    Tolin S,De Franceschi G,Spolaore B,Frare E,Canton M,Polverino de Laureto P,Fontana A. The oleic acid complexes of proteolytic fragments of α-lactalbumin display apoptotic activity. FEBS J 2010; 277: 163–173.
    Direct Link:
  • 13
    Atri MS,Sabouty AA,Moosavi-Movahedi AA,Goliaei B,Sefidbakht Y,Alijanvand HH,Sharifzadeh A,Niasari-Naslaji A. Structure and stability analysis of cytotoxic complex of camel α-lactalbumin and unsaturated fatty acids produced at high temperature. J Biomol Struct Dyn 2011; 28: 919–928.
  • 14
    Wijesinha-Bettoni R,Dobson CM,Redfield C. Comparison of the structural and dynamical properties of holo and apo bovine α-lactalbumin by NMR spectroscopy. J Mol Biol 2001; 307: 885–898.
  • 15
    Chrysina ED,Brew K,Acharya KR. Crystal structures of apo- and holo-bovine α-lactalbumin at 2.2-Å resolution reveal an effect of calcium on inter-lobe interactions. J Biol Chem 2000; 275: 37021–37029.
  • 16
    Luck JM. The combination of fatty acid anions with proteins. Discuss Faraday Soc 1949; 6: 44–52.
  • 17
    Kinnear AMG,O Kelly K,Naismith WEF. The interaction of sodium oleate with conarachin II. J Biol Chem 1958; 232: 67–73.
  • 18
    Spolaore B,Pinato O,Canton M,Zambonin M,Polverino de Laureto P,Fontana A. α-Lactalbumin forms with oleic acid a high molecular weight complex displaying cytotoxic activity. Biochemistry 2010; 49: 8658–8667.
  • 19
    Pettersson-Kastberg J,Mossberg AK,Trulsson M,Yong YJ,Min S,Lim Y,O'Brien JE,Svanborg C,Mok KH. α-Lactalbumin, engineered to be nonnative and inactive, kills tumor cells when in complex with oleic acid: a new biological function resulting from partial unfolding. J Mol Biol 2009; 394: 994–1010.
  • 20
    Wilhelm K,Darinskas A,Noppe W,Duchardt E,Mok KH,Vukojevic V,Schleucher J,Morozova-Roche LA. Protein oligomerization induced by oleic acid at the solid–liquid interface–equine lysozyme cytotoxic complexes. FEBS J 2009; 276: 3975–3989.
    Direct Link:
  • 21
    Knyazeva EL,Grishchenko VM,Fadeev RS,Akatov VS,Permyakov SE,Permyakov EA. Who is Mr. HAMLET? Interaction of human α-lactalbumin with monomeric oleic acid. Biochemistry 2008; 47: 13127–13137.
  • 22
    Baslé E,Joubert N,Pucheault M. Protein chemical modification on endogenous amino acids. Chem Biol 2010; 17: 213–227.
  • 23
    Dixon HBF,Perham RN. Reversible blocking of amino groups with citraconic anhydride. Biochem J 1968; 109: 312–314.
  • 24
    Habibi AE,Khajeh K,Nemat-Gorgani M. Chemical modification of lysine residues in Bacillus licheniformis α-amylase: conversion of an endo- to an exo- type enzyme. J Biochem Mol Biol 2004; 37: 642–647.
  • 25
    Batra PP. Regeneration of native ovalbumin conformation disrupted by citraconylation. Biochimie 1991; 73: 1397–1402.
  • 26
    Masuda T,Lde N,Kitabatake N. Effects of chemical modification of lysine residues on the sweetness of lysozyme. Chem Senses 2005; 30: 253–264.
  • 27
    Yamasaki N,Hayashi K,Funaysu M. Acetylation of lysozyme. I. Preparation, fractionation and properties of acetylated lysozyme. Agric Biol Chem 1968; 32: 55–63.
  • 28
    Cupo P,El-Deiry W,Whitney PL,Awad WM, Jr. Stabilization of proteins by guanidination. J Biol Chem 1980; 255: 10828–10833.
  • 29
    Pace CN,Vajdos F,Fee L,Grimsley G,Gray T. How to measure and predict the molar absorption coefficient of a protein. Prot Sci 1995; 4: 2411–2423.
    Direct Link:
  • 30
    Smith PK,Krohn RI,Hermanson GT,Mallia AK,Gartner FH,Provenzano MD,Fujimoto EK,Goeke NM,Olson BJ,Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem 1985; 150: 76–85.
  • 31
    Fields R. The measurement of amino groups in proteins and peptides. Biochem J 1971; 124: 581–590.
  • 32
    Couch JR,Thomas MC. A comparison of chemical methods for the determination of available lysine in various proteins. J Agric Food Chem 1976; 24: 943–946.
  • 33
    Goldfarb AR. A kinetic study of the reactions of amino acids and peptides with trinitrobenzenesulfonic acid. Biochemistry 1966; 5: 2570–2578.
  • 34
    Fast J,Mossberg AK,Nilsson H,Svanborg C,Akke M,Linse S. Compact oleic acid in HAMLET. FEBS Lett 2005; 579: 6095–6100.
  • 35
    Kuwajima K. A folding model of α-lactalbumin deduced from the three-state denaturation mechanism. J Mol Biol 1977; 114: 241–258.
  • 36
    Fraternali F,Cavallo L. Parameter optimized surfaces (POPS): analysis of key interactions and conformational changes in the ribosome. Nucl Acids Res 2002; 30: 2950–2960.
  • 37
    Cavallo L,Kleinjung J,Fraternali F. POPS: a fast algorithm for solvent accessible surface areas at atomic and residue level. Nucl Acids Res 2003; 31: 3364–3366.
  • 38
    Myer YP. Conformation of cytochromes. II. Comparative study of circular dichroism spectra, optical rotatory dispersion, and absorption spectra of horse heart cytochrome c. J Biol Chem 1968; 243: 2115–2122.
  • 39
    Louis-Jeune C,Andrade-Navarro MA,Perez-Iratxeta C. Prediction of protein secondary structure from circular dichroism using theoretically derived spectra. Proteins: Struct Funct Bioinf 2012; 80: 374–381.
    Direct Link:
  • 40
    Arai M,Kuwajima K. Role of the molten globule state in protein folding. Adv Protein Chem 2000; 53: 209–282.
  • 41
    Kuwajima, K. The molten globule state of α-lactalbumin. FASEB J 1996; 10: 102–109.
  • 42
    Brinkmann CR,Heegaard CW,Petersen TE,Jensenius JC,Thiel S. The toxicity of bovine α-lactalbumin made lethal to tumor cells is highly dependent on oleic acid and induces killing in cancer cell lines and noncancer-derived primary cells. FEBS J 2011; 278: 1955–1967.
    Direct Link:
  • 43
    Permyakov SE,Knyazeva EL,Khasanova LM,Fadeev RS,Zhadan AP,Roche-Hakansson H,Håkansson AP,Akatov VS,Permyakov EA. Oleic acid is a key cytotoxic component of HAMLET-like complexes. Biol Chem 2011; 393: 85–92.
  • 44
    Lieckfeldt R,Villalaín J,Gómez-Fernández JC,Lee G. Apparent pKa of the fatty acids within ordered mixtures of model human stratum corneum lipids. Pharm Res 1995; 12: 1614–1617.
  • 45
    Jones M.N. A theoretical approach to the binding of amphipathic molecules to globular proteins. Biochem J 1975; 151: 109–114.
  • 46
    Otzen D. Protein-surfactant interactions: a tale of many states. Biochim Biophys Acta 2011; 1814: 562–591.
  • 47
    Hamilton JA. Fatty acid interactions with proteins: what X-ray crystal and NMR solution structures tell us. Prog Lipid Res 2004; 43: 177–199.
  • 48
    Zhang Y,Cremer P.S. Interactions between macromolecules and ions: the Hofmeister series. Curr Opin Chem Biol 2006; 10: 658–663.
  • 49
    Theander K,Pugh RJ. The influence of pH and temperature on the equilibrium and dynamic surface tension of aqueous solutions of sodium oleate. J Colloid Interf Sci 2001; 239: 209–216.
  • 50
    Xu X,Yu Z,Zhu Y,Wang B. Effect of sodium oleate adsorption on the colloidal stability and zeta potential of detonation synthesized diamond particles in aqueous solutions. Diam Relat Mater 2005; 14: 206–212.
  • 51
    Moosavi-Movahedi AA,Saboury AA. Elucidation of binding sites for protein denaturation by surfactant. J Chem Soc Pak 1999; 21: 248–259.
  • 52
    Moosavi-Movahedi AA. Thermodynamics of protein denaturation by sodium dodecyl sulfate. J Iranian Chem Soc 2005; 2: 189–196.
  • 53
    Pettersson J,Mossberg AK,Svanborg C. α-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem Biophys Res Commun 2006; 345: 260–270.
  • 54
    Lišková K,Kelly AL,O'Brien N,Brodkorb A. Effect of denaturation of α-lactalbumin on the formation of BAMLET (bovine α-lactalbumin made lethal to tumor cells). J Agric Food Chem 2010; 58: 4421–4427.
  • 55
    Menéndez JA,del Mar Barbacid M,Montero S,Sevilla E,Escrich E,Solanas M,Cortés-Funes H,Colomer R. Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur J Cancer 2001; 37: 402–413.
  • 56
    Cury-Boaventura MF,Pompéia C,Curi R. Comparative toxicity of oleic acid and linoleic acid on Jurkat cells. Clin Nutr 2004; 23: 721–732.
  • 57
    Martins de Lima T,Cury-Boaventura MF,Giannocco G,Nunes MT,Curi R. Comparative toxicity of fatty acids on a macrophage cell line (J 774). Clin Sci 2006; 111: 307–317.
  • 58
    Harata K,Abe Y,Muraki M. Crystallographic evaluation of internal motion of human α-lactalbumin refined by full-matrix least-squares method. J Mol Biol 1999; 287: 347–358.
  • 59
    Fischer W,Gustafsson L,Mossberg AK,Gronli J,Mork S,Bjerkvig R,Svanborg C. Human α-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res 2004; 64: 2105–2112.
  • 60
    Barbana C,Pérez MD,Sánchez L,Dalgalarrondo M,Chobert JM,Haertlé T,Calvo M. Interaction of bovine α-lactalbumin with fatty acids as determined by partition equilibrium and fluorescence spectroscopy. Int Dairy J 2006; 16: 18–25.
  • 61
    Tsuge H,Ago H,Noma M,Nitta K,Sugai S,Miyano M. Crystallographic studies of a calcium binding lysozyme from equine milk at 2.5 Å resolution. J Biochem 1992; 111: 141–143.
  • 62
    Nielsen SB,Wilhelm K,Vad B,Schleucher J,Morozova-Roche LA,Otzen D. The interaction of equine lysozyme: oleic acid complexes with lipid membranes suggests a cargo off-loading mechanism. J Mol Biol 2010; 398: 351–361.
  • 63
    Vukojevic V,Bowen AM,Wilhelm K,Ming Y,Ce Z,Schleucher J,Hore PJ,Terenius L,Morozova-Roche LA. Lipoprotein complex of equine lysozyme with oleic acid (ELOA) interactions with the plasma membrane of live cells. Langmuir 2010; 26: 14782–14787.
  • 64
    Loch J,Polit A,Górecki A,Bonarek P,Kurpiewska K,Dziedzicka-Wasylewska M,Lewinski K. Two modes of fatty acid binding to bovine β-lactoglobulin-crystallographic and spectroscopic studies. J Mol Recognit 2011; 24: 341–349.
    Direct Link:
  • 65
    Ragona L,Fogolari F,Zetta L,Pérez DM,Puyol P,De Kruif K,Löhr F,Rüterjans H,Molinari H. Bovine β-lactoglobulin: interaction studies with palmitic acid. Prot Sci 2000; 9: 1347–1356.
    Direct Link:
  • 66
    Lišková K,Auty MAE,Chaurin V,Min S,Mok KH,O'Brien N,Kelly AL,Brodkorb A. Cytotoxic complexes of sodium oleate with β-lactoglobulin. Eur J Lipid Sci Technol 2011; 113: 1207–1218.
    Direct Link:
  • 67
    Pérez MD,Díza de Villegas C,Sánchez L,Aranda P,Ena JM,Calvo M. Interaction of fatty acids with β-lactoglobulin and albumin from ruminant milk. J Biochem 1989; 106: 1094–1097.
  • 68
    Spector AA,Fletcher JE. Binding of long chain fatty acids to beta-lactoglobulin. Lipids 1970; 5: 403–411.
  • 69
    Pérez MD,Calvo M. Interaction of β-lactoglobulin with retinol and fatty acids and its role as a possible biological function for this protein: a review. J Dairy Sci 1995; 78: 978–988.
  • 70
    Sriram R,Kreutzer U,Shih L,Jue T. Interaction of fatty acid with myoglobin. FEBS Lett 2008; 582: 3643–3649.
  • 71
    Gloster J,Harris P. Fatty acid binding to cytoplasmic proteins of myocardium and red and white skeletal muscle in the rat. A possible new role for myoglobin. Biochem Biophys Res Commun 1977; 74: 506–513.
  • 72
    Vaney MC,Maignan S,Riès-Kautt M,Ducriux A. High-resolution structure (1.33 Å) of a HEW lysozyme tetragonal crystal grown in the APCF apparatus. Data and structural comparison with a crystal grown under microgravity from spacehab-01 mission. Acta Cryst 1996; D52: 505–517.
  • 73
    Yoo HA,Choi HK,Park TG. Protein-fatty acid complex for enhanced loading and stability within biodegradable nanoparticles. J Pharm Sci 2001; 90: 194–201.
    Direct Link:
  • 74
    Li Y,Jiang H,Zhu K. Encapsulation and controlled release of lysozyme from electrospun poly (ε-caprolactone)/poly (ethylene glycol) non-woven membranes by formation of lysozyme-oleate complexes. J Mater Sci: Mater Med 2008; 19: 827–832.
  • 75
    Bushnell GW,Louie GV,Brayer GD. High-resolution three-dimensional structure of horse heart cytochrome c. J Mol Biol 1990; 214: 585–595.
  • 76
    Sinibaldi F,Mei G,Polticelli F,Piro MC,Howes BD,Smulevich G,Santucci R,Ascoli F,Fiorucci L. ATP specifically drives refolding of non-native conformations of cytochrome c. Prot Sci 2005; 14: 1049–1058.
    Direct Link:
  • 77
    Tuominen EKJ,Wallace CJA,Kinnunen PKJ. Phospholipid-cytochrome c interaction evidence for the extended lipid anchorage. JBiol Chem 2002; 277: 8822–8826.
View Full Article (HTML) Get PDF (604K)