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Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease

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Abstract

Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The hexapeptide stretch 21DIDLHL26 has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85α subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of chicken brain α-spectrin, which is otherwise non-amyloidogenic, is rendered amyloidogenic if 22EVTMKK27 is replaced by DIDLHL. In this article, we describe the aggregation behaviour of DIDLHL-COOH and DIDLHL-CONH2. Our results indicate that DIDLHL-COOH and DIDLHL-CONH2 aggregate to form spherical structures at pH 5 and 6. At pH 5, in the presence of mica, DIDLHL-CONH2 forms short fibrous structures. The presence of NaCl along with mica results in fibrillar structures. At pH 6, DIDLHL-CONH2 forms largely spherical aggregates. Both the peptides are unstructured in solution but adopt β-conformation on drying. The aggregates formed by DIDLHL-COOH and DIDLHL-CONH2 are formed during drying process and their structures are modulated by the presence of mica and salt. Our study suggests that a peptide need not have intrinsic amyloidogenic propensity to facilitate the self-assembly of the full-length protein. The propensity of peptides to form self-assembled structures that are non-amyloidogenic could be important in potentiating the self-assembly of full-length proteins into amyloid fibrils.

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Abbreviations

AFM:

atomic force microscopy

ATR:

attenuated total reflection

CD:

circular dichroism

D-ac:

NH2−DIDLHL−COOH

D-am:

NH2−DIDLHL−CONH2

FTIR:

Fourier transform infrared

MALDI TOF:

matrix-assisted laser desorption ionization time-of-flight

PI3-SH3:

phosphatidylinositol-3-kinase

SH3:

Src homology 3

SPC-SH3:

SH3 domain of chicken brain α-spectrin

TFA:

trifluoroacetic acid

References

  • Anderson M, Bocharova OV, Makarava N, Breydo L, Salnikov VV and Baskakov IV 2006 Polymorphism and ultrastructural organization of prion protein amyloid fibrils: an insight from high resolution atomic force microscopy. J. Mol. Biol. 358 580–596

    Article  PubMed  CAS  Google Scholar 

  • Atherton E 1989 Solid phase synthesis: A practical approach (Oxford: IRL Press)

    Google Scholar 

  • Bauer HH, Aebi U, Haner M, Hermann R, Muller M and Merkle HP 1995 Architecture and polymorphism of fibrillar supramolecular assemblies produced by in vitro aggregation of human calcitonin. J Struct Biol 115 1–15

    Article  PubMed  CAS  Google Scholar 

  • Blackley HK, Sanders GH, Davies MC, Roberts CJ, Tendler SJ and Wilkinson MJ 2000 In-situ atomic force microscopy study of beta-amyloid fibrillization. J. Mol. Biol. 298 833–840

    Article  PubMed  CAS  Google Scholar 

  • Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, et al. 1992 Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J. Biol. Chem. 267 546–554

    PubMed  CAS  Google Scholar 

  • Chaudhary N, Singh S and Nagaraj R 2008 Organic solvent mediated self-association of an amyloid forming peptide from beta2-microglobulin: an atomic force microscopy study. Biopolymers 90 783–791

    Article  PubMed  CAS  Google Scholar 

  • Chaudhary N, Singh S and Nagaraj R 2009 Morphology of self-assembled structures formed by short peptides from the amyloidogenic protein tau depends on the solvent in which the peptides are dissolved. J. Pept. Sci. 15 675–684

    Article  PubMed  CAS  Google Scholar 

  • Chiba T, Hagihara Y, Higurashi T, Hasegawa K, Naiki H and Goto Y 2003 Amyloid fibril formation in the context of full-length protein: effects of proline mutations on the amyloid fibril formation of beta2-microglobulin. J. Biol. Chem. 278 47016–47024

    Article  PubMed  CAS  Google Scholar 

  • Fandrich M, Fletcher MA and Dobson CM 2001 Amyloid fibrils from muscle myoglobin. Nature (London) 410 165–166

    Article  CAS  Google Scholar 

  • Fandrich M, Forge V, Buder K, Kittler M, Dobson CM and Diekmann S 2003 Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments. Proc. Natl. Acad. Sci. USA 100 15463–15468

    Google Scholar 

  • Fezoui Y, Hartley DM, Walsh DM, Selkoe DJ, Osterhout JJ and Teplow DB 2000 A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils. Nat. Struct. Biol. 7 1095–1099

    Article  PubMed  CAS  Google Scholar 

  • Giasson BI, Murray IV, Trojanowski JQ and Lee VM 2001 A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J. Biol. Chem. 276 2380–2386

    Article  PubMed  CAS  Google Scholar 

  • Gnanakaran S, Nussinov R and Garcia AE 2006 Atomic-level description of amyloid beta-dimer formation. J. Am. Chem. Soc. 128 2158–2159

    Article  PubMed  CAS  Google Scholar 

  • Goldsbury C, Frey P, Olivieri V, Aebi U and Muller SA 2005 Multiple assembly pathways underlie amyloid-beta fibril polymorphisms. J. Mol. Biol. 352 282–298

    Article  PubMed  CAS  Google Scholar 

  • Gorbitz CH 2001 Nanotube formation by hydrophobic dipeptides. Chemistry – Eur. J. 7 5153–5159

  • Goux WJ, Kopplin L, Nguyen AD, Leak K, Rutkofsky M, Shanmuganandam VD, Sharma D, Inouye H, et al. 2004 The formation of straight and twisted filaments from short tau peptides. J. Biol. Chem. 279 26868–26875

    Article  PubMed  CAS  Google Scholar 

  • Guijarro JI, Sunde M, Jones JA, Campbell ID and Dobson CM 1998 Amyloid fibril formation by an SH3 domain. Proc. Natl. Acad. Sci. USA 95 4224–4228

    Google Scholar 

  • Haris PI and Chapman D 1995 The conformational analysis of peptides using Fourier transform IR spectroscopy. Biopolymers 37 251–263

    Article  PubMed  CAS  Google Scholar 

  • Harper JD, Wong SS, Lieber CM and Lansbury PT Jr 1999 Assembly of A beta amyloid protofibrils: an in vitro model for a possible early event in Alzheimer's disease. Biochemistry 38 8972–8980

    Article  PubMed  CAS  Google Scholar 

  • Iconomidou VA, Chryssikos GD, Gionis V, Vriend G, Hoenger A and Hamodrakas SJ 2001 Amyloid-like fibrils from an 18-residue peptide analogue of a part of the central domain of the B-family of silkmoth chorion proteins. FEBS Lett. 499 268–273

    Google Scholar 

  • Iconomidou VA, Vriend G and Hamodrakas SJ 2000 Amyloids protect the silkmoth oocyte and embryo. FEBS Lett. 479 141–145

    Google Scholar 

  • Ivanova MI, Sawaya MR, Gingery M, Attinger A and Eisenberg D 2004 An amyloid-forming segment of beta2-microglobulin suggests a molecular model for the fibril. Proc. Natl. Acad. Sci. USA 101 10584–10589

    Google Scholar 

  • Ivanova MI, Thompson MJ and Eisenberg D 2006 A systematic screen of beta(2)-microglobulin and insulin for amyloid-like segments. Proc. Natl. Acad. Sci. USA 103 4079–4082

    Google Scholar 

  • Jackson M and Mantsch HH 1995 The use and misuse of FTIR spectroscopy in the determination of protein structure. Crit. Rev. Biochem. Mol. Biol. 30 95–120

    Article  PubMed  CAS  Google Scholar 

  • Jansen R, Dzwolak W and Winter R 2005 Amyloidogenic self-assembly of insulin aggregates probed by high resolution atomic force microscopy. Biophys. J. 88 1344–1353

    Article  PubMed  CAS  Google Scholar 

  • Jarvis JA, Craik DJ and Wilce MC 1993 X-ray diffraction studies of fibrils formed from peptide fragments of transthyretin. Biochem. Biophys. Res. Commun. 192 991–998

    Article  PubMed  CAS  Google Scholar 

  • Jones S, Manning J, Kad NM and Radford SE 2003 Amyloid-forming peptides from beta2-microglobulin-Insights into the mechanism of fibril formation in vitro. J. Mol. Biol. 325 249–257

    Article  PubMed  CAS  Google Scholar 

  • Kad NM, Thomson NH, Smith DP, Smith DA and Radford SE 2001 Beta(2)-microglobulin and its deamidated variant, N17D form amyloid fibrils with a range of morphologies in vitro. J. Mol. Biol. 313 559–571

    Article  PubMed  CAS  Google Scholar 

  • Kardos J, Okuno D, Kawai T, Hagihara Y, Yumoto N, Kitagawa T, Zavodszky P, Naiki H, et al. 2005 Structural studies reveal that the diverse morphology of beta(2)-microglobulin aggregates is a reflection of different molecular architectures. Biochim. Biophys. Acta 1753 108–120

    Google Scholar 

  • King DS, Fields CG and Fields GB 1990 A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis. Int. J. Pept. Protein Res. 36 255–266

    Google Scholar 

  • Kortemme T, Kelly MJ, Kay LE, Forman-Kay J and Serrano L 2000 Similarities between the spectrin SH3 domain denatured state and its folding transition state. J. Mol. Biol. 297 1217–1229

    Article  PubMed  CAS  Google Scholar 

  • Kozhukh GV, Hagihara Y, Kawakami T, Hasegawa K, Naiki H and Goto Y 2002 Investigation of a peptide responsible for amyloid fibril formation of beta 2-microglobulin by achromobacter protease I. J. Biol. Chem. 277 1310–1315

    Article  PubMed  CAS  Google Scholar 

  • Lopez De La Paz M, Goldie K, Zurdo J, Lacroix E, Dobson CM, Hoenger A and Serrano L 2002 De novo designed peptide-based amyloid fibrils. Proc. Natl. Acad. Sci. USA 99 16052–16057

    Google Scholar 

  • Losic D, Martin LL, Aguilar MI and Small DH 2006 Beta-amyloid fibril formation is promoted by step edges of highly oriented pyrolytic graphite. Biopolymers 84 519–526

    Article  PubMed  CAS  Google Scholar 

  • Morel B, Casares S and Conejero-Lara F 2006 A single mutation induces amyloid aggregation in the alpha-spectrin SH3 domain: analysis of the early stages of fibril formation. J. Mol. Biol. 356 453–468

    Article  PubMed  CAS  Google Scholar 

  • Paravastu AK, Petkova AT and Tycko R 2006 Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid peptide. Biophys. J. 90 4618–4629

    Article  PubMed  CAS  Google Scholar 

  • Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP and Tycko R 2005 Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. Science 307 262–265

    Article  PubMed  CAS  Google Scholar 

  • Reches M and Gazit E 2003 Casting metal nanowires within discrete self-assembled peptide nanotubes. Science 300 625–627

    Article  PubMed  CAS  Google Scholar 

  • Reches M and Gazit E 2006 Designed aromatic homo-dipeptides: formation of ordered nanostructures and potential nanotechnological applications. Phys. Biol. 3 S10–19

    Article  PubMed  CAS  Google Scholar 

  • Reches M, Porat Y and Gazit E 2002 Amyloid fibril formation by pentapeptide and tetrapeptide fragments of human calcitonin. J. Biol. Chem. 277 35475–35480

    Article  PubMed  CAS  Google Scholar 

  • Surewicz WK, Mantsch HH and Chapman D 1993 Determination of protein secondary structure by Fourier transform infrared spectroscopy: a critical assessment. Biochemistry 32 389–394

    Article  PubMed  CAS  Google Scholar 

  • Tenidis K, Waldner M, Bernhagen J, Fischle W, Bergmann M, Weber M, Merkle ML, Voelter W, et al. 2000 Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties. J. Mol. Biol. 295 1055–1071

    Article  PubMed  CAS  Google Scholar 

  • Thompson A, White AR, McLean C, Masters CL, Cappai R and Barrow CJ 2000 Amyloidogenicity and neurotoxicity of peptides corresponding to the helical regions of PrP(C). J. Neurosci. Res. 62 293–301

    Article  PubMed  CAS  Google Scholar 

  • Thompson MJ, Sievers SA, Karanicolas J, Ivanova MI, Baker D and Eisenberg D 2006 The 3D profile method for identifying fibril-forming segments of proteins. Proc. Natl. Acad. Sci. USA 103 4074–4078

    Google Scholar 

  • Tjernberg L, Hosia W, Bark N, Thyberg J and Johansson J 2002 Charge attraction and beta propensity are necessary for amyloid fibril formation from tetrapeptides. J. Biol. Chem. 277 43243–43246

    Article  PubMed  CAS  Google Scholar 

  • Tracz SM, Abedini A, Driscoll M and Raleigh DP 2004 Role of aromatic interactions in amyloid formation by peptides derived from human Amylin. Biochemistry 43 15901–15908

    Article  PubMed  CAS  Google Scholar 

  • Ventura S, Zurdo J, Narayanan S, Parreno M, Mangues R, Reif B, Chiti F, Giannoni E, et al. 2004 Short amino acid stretches can mediate amyloid formation in globular proteins: the Src homology 3 (SH3) case. Proc. Natl. Acad. Sci. USA 101 7258–7263

    Google Scholar 

  • von Bergen M, Barghorn S, Biernat J, Mandelkow EM and Mandelkow E 2005 Tau aggregation is driven by a transition from random coil to beta sheet structure. Biochim. Biophys. Acta 1739 158–166

    Google Scholar 

  • von Bergen M, Barghorn S, Li L, Marx A, Biernat J, Mandelkow EM and Mandelkow E 2001 Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J. Biol. Chem. 276 48165–48174

    Google Scholar 

  • von Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow EM and Mandelkow E 2000 Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proc. Natl. Acad. Sci. USA 97 5129–5134

    Google Scholar 

  • Waddell WJ 1956 A simple ultraviolet spectrophotometric method for the determination of protein. J. Lab. Clin. Med. 48 311–314

    PubMed  CAS  Google Scholar 

  • Wolf P 1983 A critical reappraisal of Waddell's technique for ultraviolet spectrophotometric protein estimation. Anal Biochem. 129 145–155

    Google Scholar 

  • Yamaguchi K, Takahashi S, Kawai T, Naiki H and Goto Y 2005 Seeding-dependent propagation and maturation of amyloid fibril conformation. J. Mol. Biol. 352 952–960

    Article  PubMed  CAS  Google Scholar 

  • Zhu M, Souillac PO, Ionescu-Zanetti C, Carter SA and Fink AL 2002 Surface-catalyzed amyloid fibril formation. J. Biol. Chem. 277 50914–50922

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was funded by CSIR under the Network Project NWP035.

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Authors and Affiliations

  1. CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India

    Nitin Chaudhary, Shashi Singh & Ramakrishnan Nagaraj

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  1. Nitin Chaudhary
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  2. Shashi Singh
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  3. Ramakrishnan Nagaraj
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Correspondence to Ramakrishnan Nagaraj.

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Corresponding editor: MarÍa Eliano Lanio

[Chaudhary N, Singh S and Nagaraj R 2011 Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease. J. Biosci. 36 679–689] DOI 10.1007/s12038-011-9104-3

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Chaudhary, N., Singh, S. & Nagaraj, R. Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease. J Biosci 36, 679–689 (2011). https://doi.org/10.1007/s12038-011-9104-3

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