Abstract
The formation offilamentsandfibrilsbyspecificpeptidesubstratesis widespreadinnatureandunderliesthepathologyofdiseasessuchas Alzheimer’s and Creutzfelt Jacob (CJD). These processes result from a conformationalswitch which allows polymerisation of the protein usually into highly stable β sheet structures. Here we describe the properties of a peptide derived from a 24 amino acid motif called a leucine rich repeat which under goes such a structural transition. We show that a conserved amide sidechain is required for filament formation and contrast this with the role played by these residues in the native structures of LRR proteins. Interestingly, mutations involving amide residues are often associated with amyloid disease, including predispositions to sporadic CJD. We also describe studies of early events infilament formation by both the LRR peptide and a derivative of Alzheimer β protein 1–42 using the technique of time resolved fluorescent anisotropy.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aggeli, A., Bell, M., Boden, N., Keen, J.N., Knowles, P.F., McLeish, T.C.B., Pitkeathly, M. and Radford, S.E. (1997) Responsive gels formed by spontaneous self assembly of peptidesinto polymeric beta-sheet tapes. Nature 386, 259–262.
Buchanan, S.G.S.C. and Gay, N.J. (1996) Structural and functional diversity in the leucine rich repeat family of proteins. Prog. Biophys. Mol. Biol. 65, 1–44.
Chuang, T.J. and Eisenthal, K.B. (1972) Theory of fluorescence depolarisation by anisotropic rotational diffusion. J. Chem. Phys. 57, 5094–5097.
Denny, R. C. (1993) The CCP13 Newsletter No. 2 (Daresbury Laboratory, Warrington U.K.)
Diggle, C., Hutton, M., Jones, G.R., Thomas, C.M., and Jackson, J.B. (1995) Properties of The Soluble Polypeptide of The Proton-Translocating Transhydrogenase From Rhodospirillum-Rubrum Obtained By Expression In Escherichia-Coli. European Journal of Biochemistry 228, 719.
Fraser, P.E. Nguyen, J. T., Surewicz E. K and Kirschner, D. A. (1991) pH dependent structural transitions of Alzheimer amyloid peptides. Biophys. J. 60, 1190–1201.
Gay, N.J., Packman, L.C., Weldon, M.A. and Barna, J.C.J. (1991) A leucine rich repeat peptide derived from the Drosophila Toll receptorforms extended filaments with a β-sheet structure. FEBS Lett. 291, 87–91.
Geddes, A. J., Parker, K. D. Atkins, E. D. T., and Beighton, E. (1968) “Cross-β” conformation in proteins J. Mol. Biol. 32, 343–358.
Ghiso, J., Jensson, O. and Frangione, B. (1986) Amyloid fibrils in hereditary haemorrhage with amyloidosis of Icelandic type is a variant of γ trace basic protein (cystatin C). Proc. Natl. Acad. Sci. (USA) 83, 2974–2978.
Goldfarb, L.G., Petersen, R.B., Tabaton, M., Brown, P., Leblanc, A.C., Montagna, P., Cortelli, P., Julien, J., Vital, C., Pendlebury, W.W., Haltia, M., Wills, P.R., Hauw, J.J., McKeever, P.E., Monari, L., Schrank, B., Swergold, G.D., Autiliogambetti, L., Gajdusek, D.C., Lugaresi, E. and Gambetti, P.(1992) Fatal familial in somnia and familial Creutzfeldt-Jakobdisease-disease phenotype determined by a DNA polymorphism. Science 258, 806–808.
Inouye, H., Fraser, P.E. and Kirschner, D.A.(1993) Structure of β-crystalline assemblies formed by Alzheimer β-amyloid protein analogues: analysis by X-ray diffraction. Biophys. J. 64, 502–519.
Kirschner, D. A. Abraham, C. and Selkoe, D. J. (1986) X-ray diffraction from interneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates a cross-β conformation. Proc Natl Acad Sci USA 83, 503–507.
Kirschner, D. A. Inouye, H., Duffy, L. K., Sinclair, A., Lind, M. and Selkoe, D. J. (1987) Synthetic homologues to protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc Natl Acad Sci USA 84 6953–6957.
Kobe, B. and Deisenhofer, J. (1993) Crystal structure of porcine ribonuclease inhibitor, a protein with leucine rich repeats. Nature 366, 751–756.
Kobe, B. and Deisenhofer, J. (1995) Proteins with leucine rich repeats. Curr. Opin. Struct. Biol. 5, 409–416.
Kunisada, K., Higuchi, K., Shin-ichi, A. and Yamagishi, H. (1986) Molecular cloning and nucleotide sequencing of cDNA for murine senile amyloid protein: nucleotide substitutions found in apolipoprotein A-II cDNA of senescence accelerated mouse. Nucl. Acids. Res. 14, 5929–5939.
Lakowicz, J.R., Principles of Fluorescence Spectrocopy (Plenum, New York, 1983).
Lansbury, P.J. and Jarret, J.T. (1993) Seeding one-dimensional crystallization of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie. Cell73, 1055–1058.
Maury, C.P.J. and Nurmiaho, E.L. (1992) Creation of amyloid fibrils by mutantasn 187 gelsolinpeptides. Biochem. Biophys. Res. Comm. 183, 227–231.
Martin-Fernandez, M.L., Tobin, M.J., Clarke, D.T., Gregory, C.M. and Jones, G.R. (1996) A high sensitivity time-resolved microfluorimeter for real-time cell biology. Rev.Sci.Ins. 67, 3716–3721.
Martin-Fernandez, M.L., Tobin, M.J., Clarke, D.T., Gregory, C.M. and Jones, G.R. (1998) Sub-nanosecond polarised microfluorimetry in the time domain: Aninstrument for studying receptor trafficking in live cells. Rev. Sci. Ins. 69, 540–543.
Nguyen, J.T., Inouye, H., Baldwin, M.A., Fletterick, R.J., Cohen, F.E., Prusiner, S.B. and Kirschner, D.A. (1995) X-ray diffraction of scrapie prion rods and PrP peptides. J. Mol. Biol. 252, 412–422.
O’Connor D.V.O., Ware, W.R., and Andre, J.C. (1979) Deconvolution of fluorescence decay curves. A critical comparison of techniques. J. Phys. Chem. 83, 1333–1343.
Perutz, M.F., Johnson, T., Suzuki, M. and Finch, J.(1994) Glutamine repeats as polarzippers: their possible role in inherited neurodegenerative diseases. Proc. Natl. Acad.Sci.USA 91, 5355–5358.
Price, S.R., Evens, P.R. and Nagai, K.(1998) Crystal structure of the spliceosomal U2B″-U2A′ protein complex bound to a fragment of U2 small nuclear RNA. Nature 394 645–650.
Shibuya, S., Higuchi, J. and Shin, R.W. (1998) Codon 219 lys allele is not found in sporadic CJD. Annals Neurol. 43, 826–828.
Soto, C., Castano, E.M., Frangione, B. and Inestrosa, N.C. (1995) The α-helical to β-strand transition in the amino terminal fragment of amyloid β-peptide modulates amyloid formation. J. Biol. Chem. 270; 3063–3067.
Srinivasan, N., Anaradha, V.S., Ramakrishnan, C., Sowdhamini, R. and Balaram, P. (1994) Conformational characteristics of asparaginyl residues in proteins. Int. J. Pept. Prot. Res. 44, 112–122.
Symmons, M.F., Buchanan, S.G., Clark, D.T., Jones, G. R. and Gay, N.J. (1997) X-ray diffraction and far UV CD studies of filaments formed by a leucine rich repeat peptide: structural similarity to the amyloid fibrils of prions and Alzheimer’s disease b protein. FEBS Lett. 291, 87–91.
Weber, G. (1971) Theory of fluorescence depolarisation by anisotropic Brownian rotations. Discontinuous distribution approach. J. Chem. Phys. 55, 2399–2407.
Westaway, D., Zuliani, V., Cooper, C.M., DaCosta, M., Neuman, S., Jenny, A.L., Detwiler, L. and Prusiner, S.B.( 1994) Homozygosity for prion protein alleles encoding glutamine 171 render sheep susceptible to natural scrapie. Genes Develop. 8, 959–969.
Yoder, F. and Jurnak, F. (1995) The parallel β-helix and other coiled folds. FASEB J. 9, 335–342.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Gay, N.J., Symmons, M., Martin-Fernandez, M., Jones, G. (2002). Structure and Stabilisation of Self-Assembling Peptide Filaments. In: Self-Assembling Peptide Systems in Biology, Medicine and Engineering. Springer, Dordrecht. https://doi.org/10.1007/0-306-46890-5_9
Download citation
DOI: https://doi.org/10.1007/0-306-46890-5_9
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-7090-1
Online ISBN: 978-0-306-46890-2
eBook Packages: Springer Book Archive