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Review Article

Can misfolded proteins be beneficial? The HAMLET case

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Pages 162-176 | Received 11 Mar 2008, Published online: 08 Jul 2009

References

  • Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973; 181: 223–30
  • Cabrita LD, Bottomley SP. How do proteins avoid becoming too stable? Biophysical studies into metastable proteins. Eur Biophys J. 2004; 33: 83–8
  • Bemporad F, Gsponer J, Hopearuoho HI, Plakoutsi G, Stati G, Stefani M, et al. Biological function in a non-native partially folded state of a protein. EMBO J. 2008; 27: 1525–35
  • Svensson M, Hakansson 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: 4221–6
  • Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW. Functional amyloid formation within mammalian tissue. PLoS Biol. 2006; 4: e6
  • Shorter J, Lindquist S. Prions as adaptive conduits of memory and inheritance. Nat Rev Genet. 2005; 6: 435–50
  • Beadle GW, Tatum EL. Genetic control of biochemical reactions in neurospora. Proc Natl Acad Sci U S A. 1941; 27: 499–506
  • Green ED, Chakravarti A. The human genome sequence expedition: views from the ‘base camp’. Genome Res. 2001; 11: 645–51
  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science. 2001; 291: 1304–51
  • International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004;431:931–45.
  • Dobson CM. Protein misfolding, evolution and disease. Trends Biochem Sci. 1999; 24: 329–32
  • Claverie JM. Gene number. What if there are only 30,000 human genes?. Science. 2001; 291: 1255–7
  • Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, et al. Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature. 2000; 406: 959–64
  • Hakansson 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: 8064–8
  • Jeffery CJ. Moonlighting proteins. Trends Biochem Sci. 1999; 24: 8–11
  • Tompa P, Szasz C, Buday L. Structural disorder throws new light on moonlighting. Trends Biochem Sci. 2005; 30: 484–9
  • Hartl FU, Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science. 2002; 295: 1852–8
  • Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell. 2006; 125: 443–51
  • Gething MJ, Sambrook J. Protein folding in the cell. Nature. 1992; 355: 33–45
  • Mok KH, Hore PJ. Photo-CIDNP NMR methods for studying protein folding. Methods. 2004; 34: 75–87
  • Dobson CM. The structural basis of protein folding and its links with human disease. Philos Trans R Soc Lond B Biol Sci. 2001; 356: 133–45
  • Vendruscolo M, Paci E, Karplus M, Dobson CM. Structures and relative free energies of partially folded states of proteins. Proc Natl Acad Sci U S A. 2003; 100: 14817–21
  • Levinthal C. Are there pathways for protein folding?. J Chim Phys. 1968; 65: 44–5
  • Dill KA, Chan HS. From Levinthal to pathways to funnels. Nat Struct Biol. 1997; 4: 10–9
  • Baldwin RL. The nature of protein folding pathways: the classical versus the new view. J Biomol NMR. 1995; 5: 103–9
  • Bryngelson JD, Onuchic JN, Socci ND, Wolynes PG. Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins. 1995; 21: 167–95
  • Soto C. Protein misfolding and disease; protein refolding and therapy. FEBS Lett. 2001; 498: 204–7
  • Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, Liu CY, et al. The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol. 2002; 3: 411–21
  • Chiti F, Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem. 2006; 75: 333–66
  • Trzesniewska K, Brzyska M, Elbaum D. Neurodegenerative aspects of protein aggregation. Acta Neurobiol Exp (Wars) 2004; 64: 41–52
  • Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, et al. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci U S A. 1988; 85: 7341–5
  • Soto C, Castano EM, Frangione B, Inestrosa NC. The α-helical to β-strand transition in the amino-terminal fragment of the amyloid ß-peptide modulates amyloid formation. J Biol Chem. 1995; 270: 3063–7
  • Barrow CJ, Yasuda A, Kenny PT, Zagorski MG. Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra. J Mol Biol. 1992; 225: 1075–93
  • Hilbich C, Kisters-Woike B, Reed J, Masters CL, Beyreuther K. Substitutions of hydrophobic amino acids reduce the amyloidogenicity of Alzheimer's disease beta A4 peptides. J Mol Biol. 1992; 228: 460–73
  • Geula C, Wu CK, Saroff D, Lorenzo A, Yuan M, Yankner BA. Aging renders the brain vulnerable to amyloid beta-protein neurotoxicity. Nat Med. 1998; 4: 827–31
  • Soto C, Sigurdsson EM, Morelli L, Kumar RA, Castano EM, Frangione B. β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat Med. 1998; 4: 822–6
  • Caughey B, Baron GS. Prions and their partners in crime. Nature. 2006; 443: 803–10
  • Prusiner SB, Scott MR, DeArmond SJ, Cohen FE. Prion protein biology. Cell. 1998 1; 93:337–48.
  • Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, et al. Conversion of a-helices into ß-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A. 1993; 90: 10962–6
  • Aguzzi A, Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol. 2006; 4: 765–75
  • Castilla J, Saa P, Hetz C, Soto C. In vitro generation of infectious scrapie prions. Cell. 2005; 121: 195–206
  • Si K, Lindquist S, Kandel ER. A neuronal isoform of the aplysia CPEB has prion-like properties. Cell. 2003; 115: 879–91
  • Lindquist S, Krobitsch S, Li L, Sondheimer N. Investigating protein conformation-based inheritance and disease in yeast. Philos Trans R Soc Lond B Biol Sci. 2001; 356: 169–76
  • Paushkin SV, Kushnirov VV, Smirnov VN, Ter-Avanesyan MD. Propagation of the yeast prion-like [psi+] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J. 1996; 15: 3127–34
  • Svensson M, Sabharwal H, Hakansson A, Mossberg AK, Lipniunas P, Leffler H, et al. Molecular characterization of alpha-lactalbumin folding variants that induce apoptosis in tumor cells. J Biol Chem. 1999; 274: 6388–96
  • Arai M, Kuwajima K. Role of the molten globule state in protein folding. Adv Protein Chem. 2000; 53: 209–82
  • Ptitsyn OB. Molten globule and protein folding. Adv Protein Chem. 1995; 47: 83–229
  • Halliburton WD. The proteids of milk. J Physiol. 1890; 11: 448–63
  • Heine WE, Klein PD, Reeds PJ. The importance of α-lactalbumin in infant nutrition. J Nutr. 1991; 121: 277–83
  • Lonnerdal B, Forsum E. Casein content of human milk. Am J Clin Nutr. 1985; 41: 113–20
  • Zweig G, Block RJ. Studies on bovine whey proteins. III. The preparation of crystalline a-lactalbumin and ß-lactoglobulin ferrilactin. Arch Biochem Biophys. 1954; 51: 200–7
  • Acharya KR, Ren JS, Stuart DI, Phillips DC, Fenna RE. Crystal structure of human α-lactalbumin at 1.7 A resolution. J Mol Biol. 1991; 221: 571–81
  • Chandra N, Brew K, Acharya KR. Structural evidence for the presence of a secondary calcium binding site in human α-lactalbumin. Biochemistry. 1998; 37: 4767–72
  • Fenna RE. Crystallization of human α-lactalbumin. J Mol Biol. 1982; 161: 211–5
  • Vanaman TC, Brew K, Hill RL. The disulfide bonds of bovine a-lactalbumin. J Biol Chem. 1970; 245: 4583–90
  • Hiraoka Y, Segawa T, Kuwajima K, Sugai S, Murai N. α-Lactalbumin: a calcium metalloprotein. Biochem Biophys Res Commun. 1980; 95: 1098–104
  • Kuwajima K. The molten globule state of α-lactalbumin. FASEB J. 1996; 10: 102–9
  • Mok KH, Nagashima T, Day IJ, Hore PJ, Dobson CM. Multiple subsets of side-chain packing in partially folded states of α-lactalbumins. Proc Natl Acad Sci U S A. 2005; 102: 8899–904
  • Peng ZY, Kim PS. A protein dissection study of a molten globule. Biochemistry. 1994; 33: 2136–41
  • Schulman BA, Redfield C, Peng ZY, Dobson CM, Kim PS. Different subdomains are most protected from hydrogen exchange in the molten globule and native states of human α-lactalbumin. J Mol Biol. 1995; 253: 651–7
  • Chyan CL, Wormald C, Dobson CM, Evans PA, Baum J. Structure and stability of the molten globule state of guinea-pig α-lactalbumin: a hydrogen exchange study. Biochemistry. 1993; 32: 5681–91
  • Polverino de Laureto P, Frare E, Gottardo R, Fontana A. Molten globule of bovine α-lactalbumin at neutral pH induced by heat, trifluoroethanol, and oleic acid: a comparative analysis by circular dichroism spectroscopy and limited proteolysis. Proteins. 2002; 49: 385–97
  • Wu LC, Peng ZY, Kim PS. Bipartite structure of the α-lactalbumin molten globule. Nat Struct Biol. 1995; 2: 281–6
  • Wu LC, Kim PS. A specific hydrophobic core in the α-lactalbumin molten globule. J Mol Biol. 1998; 280: 175–82
  • Pettersson J, Mossberg AK, Svanborg C. α-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem Biophys Res Commun. 2006; 345: 260–70
  • Chedad A, Van Dael H. Kinetics of folding and unfolding of goat α-lactalbumin. Proteins. 2004; 57: 345–56
  • Dolgikh DA, Gilmanshin RI, Brazhnikov EV, Bychkova VE, Semisotnov GV, Venyaminov S, et al. α-Lactalbumin: compact state with fluctuating tertiary structure?. FEBS Lett. 1981; 136: 311–5
  • Peng ZY, Wu LC, Schulman BA, Kim PS. Does the molten globule have a native-like tertiary fold?. Philos Trans R Soc Lond B Biol Sci. 1995; 348: 43–7
  • Permyakov SE, Uversky VN, Veprintsev DB, Cherskaya AM, Brooks CL, Permyakov EA, et al. Mutating aspartate in the calcium-binding site of α-lactalbumin: effects on the protein stability and cation binding. Protein Eng. 2001; 14: 785–9
  • Svensson M, Fast J, Mossberg AK, Duringer C, Gustafsson L, Hallgren O, et al. α-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci. 2003; 12: 2794–804
  • Wu LC, Schulman BA, Peng ZY, Kim PS. Disulfide determinants of calcium-induced packing in α-lactalbumin. Biochemistry. 1996; 35: 859–63
  • Jensen RG. The lipids in human milk. Prog Lipid Res. 1996; 35: 53–92
  • Svensson M, Mossberg AK, Pettersson J, Linse S, Svanborg C. Lipids as cofactors in protein folding: Stereo-specific lipid-protein interactions are required to form HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci. 2003; 12: 2805–14
  • Polverino de Laureto P, Scaramella E, Frigo M, Wondrich FG, De Filippis V, Zambonin M, et al. Limited proteolysis of bovine α-lactalbumin: isolation and characterization of protein domains. Protein Sci. 1999; 8: 2290–303
  • Svanborg C, Agerstam H, Aronson A, Bjerkvig R, Duringer C, Fischer W, et al. HAMLET kills tumor cells by an apoptosis-like mechanism–cellular, molecular, and therapeutic aspects. Adv Cancer Res. 2003; 88: 1–29
  • Kohler C, Gogvadze V, Hakansson A, Svanborg C, Orrenius S, Zhivotovsky B. A folding variant of human α-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. Eur J Biochem. 2001; 268: 186–91
  • Kohler C, Hakansson A, Svanborg C, Orrenius S, Zhivotovsky B. Protease activation in apoptosis induced by MAL. Exp Cell Res. 1999; 249: 260–8
  • Hallgren O, Gustafsson L, Irjala H, Selivanova G, Orrenius S, Svanborg C. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53. Apoptosis. 2006; 11: 221–33
  • Codogno P, Meijer AJ. Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ. 12 Suppl 2005; 2: 1509–18
  • Baehrecke EH. Autophagy: dual roles in life and death?. Nat Rev Mol Cell Biol. 2005; 6: 505–10
  • Debnath J, Baehrecke EH, Kroemer G. Does autophagy contribute to cell death?. Autophagy. 2005; 1: 66–74
  • Duringer C, Hamiche A, Gustafsson L, Kimura H, Svanborg C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J Biol Chem. 2003; 278: 42131–5
  • Fischer W, Gustafsson L, Mossberg AK, Gronli J, Mork S, Bjerkvig R, et al. 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: 2105–12
  • Hakansson A, Andreasson 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: 451–60
  • Wenzel T, Baumeister W. Conformational constraints in protein degradation by the 20S proteasome. Nat Struct Biol. 1995; 2: 199–204
  • Brest P, Gustafsson M, Mossberg AK, Gustafsson L, Duringer C, Hamiche A, et al. Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer Res. 2007; 67: 11327–34
  • Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg AK, Svanborg C. Treatment of skin papillomas with topical α-lactalbumin-oleic acid. N Engl J Med. 2004; 350: 2663–72
  • Mossberg AK, Wullt B, Gustafsson L, Mansson W, Ljunggren E, Svanborg C. Bladder cancers respond to intravesical instillation of HAMLET (human a-lactalbumin made lethal to tumor cells). Int J Cancer. 2007; 121: 1352–9
  • Makin OS, Atkins E, Sikorski P, Johansson J, Serpell LC. Molecular basis for amyloid fibril formation and stability. Proc Natl Acad Sci U S A. 2005; 102: 315–20
  • Fernandez A, Berry RS. Proteins with H-bond packing defects are highly interactive with lipid bilayers: implications for amyloidogenesis. Proc Natl Acad Sci U S A. 2003; 100: 2391–6
  • Sparr E, Engel MF, Sakharov DV, Sprong M, Jacobs J, de Kruijff B, et al. Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers. FEBS Lett. 2004; 577: 117–20
  • Zhao H, Jutila A, Nurminen T, Wickstrom SA, Keski-Oja J, Kinnunen PK. Binding of endostatin to phosphatidylserine-containing membranes and formation of amyloid-like fibers. Biochemistry. 2005; 44: 2857–63
  • Zhao H, Tuominen EK, Kinnunen PK. Formation of amyloid fibers triggered by phosphatidylserine-containing membranes. Biochemistry. 2004; 43: 10302–7
  • Utsugi T, Schroit AJ, Connor J, Bucana CD, Fidler IJ. Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes. Cancer Res. 1991; 51: 3062–6
  • Dobson CM. Protein folding and misfolding. Nature. 2003; 426: 884–90
  • Fasano C, Campana V, Zurzolo C. Prions: protein only or something more? Overview of potential prion cofactors. J Mol Neurosci. 2006; 29: 195–214
  • Silveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL, Hayes SF, et al. The most infectious prion protein particles. Nature. 2005; 437: 257–61
  • Gharibyan AL, Zamotin V, Yanamandra K, Moskaleva OS, Margulis BA, Kostanyan IA, et al. Lysozyme amyloid oligomers and fibrils induce cellular death via different apoptotic/necrotic pathways. J Mol Biol. 2007; 365: 1337–49
  • Goers J, Permyakov SE, Permyakov EA, Uversky VN, Fink AL. Conformational prerequisites for α-lactalbumin fibrillation. Biochemistry. 2002; 41: 12546–51
  • Yang F, Jr, Zhang M, Zhou BR, Chen J, Liang Y. Oleic acid inhibits amyloid formation of the intermediate of α-lactalbumin at moderately acidic pH. J Mol Biol. 2006; 362: 821–34
  • Zhao H, Sood R, Jutila A, Bose S, Fimland G, Nissen-Meyer J, et al. Interaction of the antimicrobial peptide pheromone plantaricin A with model membranes: implications for a novel mechanism of action. Biochim Biophys Acta. 2006; 1758: 1461–74
  • Hakansson A, Svensson M, Mossberg AK, Sabharwal H, Linse S, Lazou I, et al. A folding variant of α-lactalbumin with bactericidal activity against Streptococcus pneumoniae. Molecular microbiology. 2000; 35: 589–600
  • Mok KH, Pettersson J, Orrenius S, Svanborg C. HAMLET, protein folding, and tumor cell death. Biochem Biophys Res Commun. 2007; 354: 1–7
  • Ren J, Stuart DI, Acharya KR. α-lactalbumin possesses a distinct zinc binding site. J Biol Chem. 1993; 268: 19292–8
  • 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. 1997; 272: 7140–50
  • Koradi R, Billeter M, Wuthrich K. MOLMOL: a program for display and analysis of macromolecular structures. J Mol Graph. 1996;14:51–5, 29–32.

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