Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization

Herrera MG, Zamarreno F, Costabel M, Ritacco H, Hütten A, Sewald N, Dodero VI (2014)
Biopolymers 101(1): 96-106.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Herrera, Maria G.; Zamarreno, Fernando; Costabel, Marcelo; Ritacco, Hernan; Hütten, AndreasUniBi; Sewald, NorbertUniBi ; Dodero, Veronica I.
Abstract / Bemerkung
Gliadin, a protein present in wheat, rye, and barley, undergoes incomplete enzymatic degradation during digestion, producing an immunogenic 33-mer peptide, LQLQPF(PQPQLPY)(3)PQPQPF. The special features of 33-mer that provoke a break in its tolerance leading to gliadin sensitivity and celiac disease remains elusive. Herein, it is reported that 33-mer gliadin peptide was not only able to fold into polyproline II secondary structure but also depending on concentration resulted in conformational transition and self-assembly under aqueous condition, pH 7.0. A 33-mer dimer is presented as one initial possible step in the self-assembling process obtained by partial electrostatics charge distribution calculation and molecular dynamics. In addition, electron microscopy experiments revealed supramolecular organization of 33-mer into colloidal nanospheres. In the presence of 1 mM sodium citrate, 1 mM sodium borate, 1 mM sodium phosphate buffer, 15 mM NaCl, the nanospheres were stabilized, whereas in water, a linear organization and formation of fibrils were observed. It is hypothesized that the self-assembling process could be the result of the combination of hydrophobic effect, intramolecular hydrogen bonding, and electrostatic complementarity due to 33-mer's high content of proline and glutamine amino acids and its calculated nonionic amphiphilic character. Although, performed in vitro, these experiments have revealed new features of the 33-mer gliadin peptide that could represent an important and unprecedented event in the early stage of 33-mer interaction with the gut mucosa prior to onset of inflammation. Moreover, these findings may open new perspectives for the understanding and treatment of gliadin intolerance disorders. (c) 2013 Wiley Periodicals, Inc. Biopolymers 101: 96-106, 2014.
circular dichroism; 33-mer gliadin peptide; supramolecular organization; electron microscopy; gliadin intolerance
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Herrera MG, Zamarreno F, Costabel M, et al. Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization. Biopolymers. 2014;101(1):96-106.
Herrera, M. G., Zamarreno, F., Costabel, M., Ritacco, H., Hütten, A., Sewald, N., & Dodero, V. I. (2014). Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization. Biopolymers, 101(1), 96-106. doi:10.1002/bip.22288
Herrera, M. G., Zamarreno, F., Costabel, M., Ritacco, H., Hütten, A., Sewald, N., and Dodero, V. I. (2014). Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization. Biopolymers 101, 96-106.
Herrera, M.G., et al., 2014. Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization. Biopolymers, 101(1), p 96-106.
M.G. Herrera, et al., “Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization”, Biopolymers, vol. 101, 2014, pp. 96-106.
Herrera, M.G., Zamarreno, F., Costabel, M., Ritacco, H., Hütten, A., Sewald, N., Dodero, V.I.: Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization. Biopolymers. 101, 96-106 (2014).
Herrera, Maria G., Zamarreno, Fernando, Costabel, Marcelo, Ritacco, Hernan, Hütten, Andreas, Sewald, Norbert, and Dodero, Veronica I. “Circular Dichroism and Electron Microscopy Studies In Vitro of 33-mer Gliadin Peptide Revealed Secondary Structure Transition and Supramolecular Organization”. Biopolymers 101.1 (2014): 96-106.

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Gómez Castro MF, Miculán E, Herrera MG, Ruera C, Perez F, Prieto ED, Barrera E, Pantano S, Carasi P, Chirdo FG., Front Immunol 10(), 2019
PMID: 30761127
Translational Chemistry Meets Gluten-Related Disorders.
Lammers KM, Herrera MG, Dodero VI., ChemistryOpen 7(3), 2018
PMID: 29531885
Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration.
Bruun SW, Josefsen K, Tanassi JT, Marek A, Pedersen MH, Sidenius U, Haupt-Jorgensen M, Antvorskov JC, Larsen J, Heegaard NH, Buschard K., J Diabetes Res 2016(), 2016
PMID: 27795959
Self-assembly of 33-mer gliadin peptide oligomers.
Herrera MG, Benedini LA, Lonez C, Schilardi PL, Hellweg T, Ruysschaert JM, Dodero VI., Soft Matter 11(44), 2015
PMID: 26376290

72 References

Daten bereitgestellt von Europe PubMed Central.

Alberts, 2008
Initial sequencing and analysis of the human genome.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J; International Human Genome Sequencing Consortium., Nature 409(6822), 2001
PMID: 11237011

Lin, Ann Phys 524(), 2012
Protein aggregation diseases: pathogenicity and therapeutic perspectives.
Aguzzi A, O'Connor T., Nat Rev Drug Discov 9(3), 2010
PMID: 20190788
Gain of function of mutant p53 by coaggregation with multiple tumor suppressors.
Xu J, Reumers J, Couceiro JR, De Smet F, Gallardo R, Rudyak S, Cornelis A, Rozenski J, Zwolinska A, Marine JC, Lambrechts D, Suh YA, Rousseau F, Schymkowitz J., Nat. Chem. Biol. 7(5), 2011
PMID: 21445056
Celiac disease.
Rubio-Tapia A, Murray JA., Curr. Opin. Gastroenterol. 26(2), 2010
PMID: 20040864
Structural basis for gluten intolerance in celiac sprue.
Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C., Science 297(5590), 2002
PMID: 12351792
Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue.
Shan L, Qiao SW, Arentz-Hansen H, Molberg O, Gray GM, Sollid LM, Khosla C., J. Proteome Res. 4(5), 2005
PMID: 16212427
The immunology of gluten sensitivity: beyond the gut.
Hadjivassiliou M, Williamson CA, Woodroofe N., Trends Immunol. 25(11), 2004
PMID: 15489185
Mechanisms of epithelial translocation of the alpha(2)-gliadin-33mer in coeliac sprue.
Schumann M, Richter JF, Wedell I, Moos V, Zimmermann-Kordmann M, Schneider T, Daum S, Zeitz M, Fromm M, Schulzke JD., Gut 57(6), 2008
PMID: 18305066
Biomolecular studies by circular dichroism.
Dodero VI, Quirolo ZB, Sequeira MA., Front Biosci (Landmark Ed) 16(), 2011
PMID: 21196159
Investigating by CD the molecular mechanism of elasticity of elastomeric proteins.
Bochicchio B, Pepe A, Tamburro AM., Chirality 20(9), 2008
PMID: 18293367
Host-guest study of left-handed polyproline II helix formation.
Kelly MA, Chellgren BW, Rucker AL, Troutman JM, Fried MG, Miller AF, Creamer TP., Biochemistry 40(48), 2001
PMID: 11724549
Aggregation and neurotoxicity of mutant amyloid beta (A beta) peptides with proline replacement: importance of turn formation at positions 22 and 23.
Morimoto A, Irie K, Murakami K, Ohigashi H, Shindo M, Nagao M, Shimizu T, Shirasawa T., Biochem. Biophys. Res. Commun. 295(2), 2002
PMID: 12150948
Supramolecular properties of the proline-rich gamma-Zein N-terminal domain.
Kogan MJ, Dalcol I, Gorostiza P, Lopez-Iglesias C, Pons R, Pons M, Sanz F, Giralt E., Biophys. J. 83(2), 2002
PMID: 12124299
Mechanism of cis-inhibition of polyQ fibrillation by polyP: PPII oligomers and the hydrophobic effect.
Darnell GD, Derryberry J, Kurutz JW, Meredith SC., Biophys. J. 97(8), 2009
PMID: 19843462
Glutamine repeats and neurodegenerative diseases: molecular aspects.
Perutz MF., Trends Biochem. Sci. 24(2), 1999
PMID: 10098399
Glutamine repeats and inherited neurodegenerative diseases: molecular aspects.
Perutz MF., Curr. Opin. Struct. Biol. 6(6), 1996
PMID: 8994886
On (GGLGY) synthetic repeating sequences of lamprin and analogous sequences.
Bochicchio B, Pepe A, Tamburro AM., Matrix Biol. 20(4), 2001
PMID: 11470400
Hierarchical self-assembly of chiral rod-like molecules as a model for peptide beta -sheet tapes, ribbons, fibrils, and fibers.
Aggeli A, Nyrkova IA, Bell M, Harding R, Carrick L, McLeish TC, Semenov AN, Boden N., Proc. Natl. Acad. Sci. U.S.A. 98(21), 2001
PMID: 11592996
Elastin: molecular description and function.
Debelle L, Tamburro AM., Int. J. Biochem. Cell Biol. 31(2), 1999
PMID: 10216959
Natural tri- to hexapeptides self-assemble in water to amyloid beta-type fiber aggregates by unexpected alpha-helical intermediate structures.
Hauser CA, Deng R, Mishra A, Loo Y, Khoe U, Zhuang F, Cheong DW, Accardo A, Sullivan MB, Riekel C, Ying JY, Hauser UA., Proc. Natl. Acad. Sci. U.S.A. 108(4), 2011
PMID: 21205900
Molecular and supramolecular structural studies on human tropoelastin sequences.
Ostuni A, Bochicchio B, Armentano MF, Bisaccia F, Tamburro AM., Biophys. J. 93(10), 2007
PMID: 17693470

Brahmachari, Biopolymers 21(), 1982

Aubry, J Am Chem Soc 107(), 1985
Turns in peptides and proteins.
Rose GD, Gierasch LM, Smith JA., Adv. Protein Chem. 37(), 1985
PMID: 2865874
Conformation of the RNA polymerase II C-terminal domain: circular dichroism of long and short fragments.
Bienkiewicz EA, Moon Woody A, Woody RW., J. Mol. Biol. 297(1), 2000
PMID: 10704311
Effect of trifluoroethanol on protein secondary structure: an NMR and CD study using a synthetic actin peptide.
Sonnichsen FD, Van Eyk JE, Hodges RS, Sykes BD., Biochemistry 31(37), 1992
PMID: 1390666
Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study.
Roccatano D, Colombo G, Fioroni M, Mark AE., Proc. Natl. Acad. Sci. U.S.A. 99(19), 2002
PMID: 12196631
Structure and modeling studies of the carboxy-terminus region of human tropoelastin.
Floquet N, Pepe A, Dauchez M, Bochicchio B, Tamburro AM, Alix AJ., Matrix Biol. 24(4), 2005
PMID: 15961300
Conformational studies of a synthetic peptide corresponding to the repeat motif of C hordein.
Tatham AS, Drake AF, Shewry PR., Biochem. J. 259(2), 1989
PMID: 2719660
A conformational study of a glutamine- and proline-rich cereal seed protein, C hordein.
Tatham AS, Drake AF, Shewry PR., Biochem. J. 226(2), 1985
PMID: 3994673
Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in vitro.
Kayed R, Bernhagen J, Greenfield N, Sweimeh K, Brunner H, Voelter W, Kapurniotu A., J. Mol. Biol. 287(4), 1999
PMID: 10191146
Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests a common, polyproline II-like conformation for bound peptides.
Jardetzky TS, Brown JH, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC., Proc. Natl. Acad. Sci. U.S.A. 93(2), 1996
PMID: 8570625
Modular binding domains in signal transduction proteins.
Cohen GB, Ren R, Baltimore D., Cell 80(2), 1995
PMID: 7834743
Structure and function of the WW domain.
Sudol M., Prog. Biophys. Mol. Biol. 65(1-2), 1996
PMID: 9029943
Classical electrostatics in biology and chemistry.
Honig B, Nicholls A., Science 268(5214), 1995
PMID: 7761829
Molecular structure of the collagen triple helix.
Brodsky B, Persikov AV., Adv. Protein Chem. 70(), 2005
PMID: 15837519
Dissection of human tropoelastin: supramolecular organization of polypeptide sequences coded by particular exons.
Pepe A, Guerra D, Bochicchio B, Quaglino D, Gheduzzi D, Pasquali Ronchetti I, Tamburro AM., Matrix Biol. 24(2), 2005
PMID: 15890261
Reversible Aggregation of alpha-Gliadin to Fibrils.
Kasarda DD, Bernardin JE, Thomas RS., Science 155(3759), 1967
PMID: 17738226

Athamneh, Smart Mater Struct 18(), 2009

Hayat, 2000

Israelachvili, 2011
Self-assembly of the amphipathic helix (VHLPPP)8. A mechanism for zein protein body formation.
Kogan MJ, Dalcol I, Gorostiza P, Lopez-Iglesias C, Pons M, Sanz F, Ludevid D, Giralt E., J. Mol. Biol. 312(5), 2001
PMID: 11580236
Assembly mechanism of recombinant spider silk proteins.
Rammensee S, Slotta U, Scheibel T, Bausch AR., Proc. Natl. Acad. Sci. U.S.A. 105(18), 2008
PMID: 18445655

Chang, Science 307(), 2005

Smoluchowski, Phys Chem (Frankfurt/Main) 92(), 1917

Nyrkova, Eur Phys J B 17(), 2000
Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis.
Ruan L, Zhang H, Luo H, Liu J, Tang F, Shi YK, Zhao X., Proc. Natl. Acad. Sci. U.S.A. 106(13), 2009
PMID: 19289834
Mechanistic investigation into the spontaneous linear assembly of gold nanospheres.
Yang M, Chen G, Zhao Y, Silber G, Wang Y, Xing S, Han Y, Chen H., Phys Chem Chem Phys 12(38), 2010
PMID: 20661507
Small globular protein motif forms particulate hydrogel under various pH conditions.
Fang J, Zhang X, Cai Y, Wei Y., Biomacromolecules 12(5), 2011
PMID: 21413697
Supramolecular non-amyloid intermediates in the early stages of α-synuclein aggregation.
Fauerbach JA, Yushchenko DA, Shahmoradian SH, Chiu W, Jovin TM, Jares-Erijman EA., Biophys. J. 102(5), 2012
PMID: 22404935
Imaging nanometer-sized α-synuclein aggregates by superresolution fluorescence localization microscopy.
Roberti MJ, Folling J, Celej MS, Bossi M, Jovin TM, Jares-Erijman EA., Biophys. J. 102(7), 2012
PMID: 22500760
The intestinal environment in health and disease - recent insights on the potential of intestinal bacteria to influence human health.
Possemiers S, Grootaert C, Vermeiren J, Gross G, Marzorati M, Verstraete W, Van de Wiele T., Curr. Pharm. Des. 15(18), 2009
PMID: 19519443
Hemopressin forms self-assembled fibrillar nanostructures under physiologically relevant conditions.
Bomar MG, Samuelsson SJ, Kibler P, Kodukula K, Galande AK., Biomacromolecules 13(3), 2012
PMID: 22304720
The structural biology of protein aggregation diseases: Fundamental questions and some answers.
Eisenberg D, Nelson R, Sawaya MR, Balbirnie M, Sambashivan S, Ivanova MI, Madsen AO, Riekel C., Acc. Chem. Res. 39(9), 2006
PMID: 16981672
Nanoparticles and the immune system.
Zolnik BS, Gonzalez-Fernandez A, Sadrieh N, Dobrovolskaia MA., Endocrinology 151(2), 2009
PMID: 20016026
Identification of the core structure of lysozyme amyloid fibrils by proteolysis.
Frare E, Mossuto MF, Polverino de Laureto P, Dumoulin M, Dobson CM, Fontana A., J. Mol. Biol. 361(3), 2006
PMID: 16859705
Mechanics of receptor-mediated endocytosis.
Gao H, Shi W, Freund LB., Proc. Natl. Acad. Sci. U.S.A. 102(27), 2005
PMID: 15972807
A self-assembling peptide acting as an immune adjuvant.
Rudra JS, Tian YF, Jung JP, Collier JH., Proc. Natl. Acad. Sci. U.S.A. 107(2), 2009
PMID: 20080728
Role of target geometry in phagocytosis.
Champion JA, Mitragotri S., Proc. Natl. Acad. Sci. U.S.A. 103(13), 2006
PMID: 16549762

Paoletti, 1997
Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins.
Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL., Proc. Natl. Acad. Sci. U.S.A. 95(11), 1998
PMID: 9600986
Structural properties and dynamic behavior of nonfibrillar oligomers formed by PrP(106-126).
Walsh P, Neudecker P, Sharpe S., J. Am. Chem. Soc. 132(22), 2010
PMID: 20465257


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