The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.

Amyloid/chemistry/toxicity; Cell Line; Cell Survival; Humans; Microscopy, Electron, Transmission; Muramidase/chemistry/toxicity; Neurons/metabolism/physiology; Protein Stability; Spectrophotometry, Infrared; Tetrazolium Salts/metabolism; Thiazoles/metabolism

Abstract :

[en] Identifying the cause of the cytotoxicity of species populated during amyloid formation is crucial to understand the molecular basis of protein deposition diseases. We have examined different types of aggregates formed by lysozyme, a protein found as fibrillar deposits in patients with familial systemic amyloidosis, by infrared spectroscopy, transmission electron microscopy, and depolymerization experiments, and analyzed how they affect cell viability. We have characterized two types of human lysozyme amyloid structures formed in vitro that differ in morphology, molecular structure, stability, and size of the cross-beta core. Of particular interest is that the fibrils with a smaller core generate a significant cytotoxic effect. These findings indicate that protein aggregation can give rise to species with different degree of cytotoxicity due to intrinsic differences in their physicochemical properties.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Mossuto, Maria F

Dhulesia, Anne

Devlin, Glyn

Frare, Erica

Kumita, Janet R

Polverino de Laureto, Patrizia

Dumoulin, Mireille ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines

Fontana, Angelo

Dobson, Christopher M

Salvatella, Xavier

Language :

English

Title :

The non-core regions of human lysozyme amyloid fibrils influence cytotoxicity.

Publication date :

2010

Journal title :

Journal of Molecular Biology

ISSN :

0022-2836

eISSN :

1089-8638

Publisher :

Academic Press, London, United Kingdom

Volume :

402

Issue :

Pages :

783-96

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954362/pdf/main.pdf

Commentary :

Available on ORBi :

since 04 November 2010

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Scopus citations^®

102

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Bibliography

Lansbury P., Lashuel H. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 2006, 443:774-779.
Haass C., Selkoe D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nat. Rev. Mol. Cell Biol. 2007, 8:101-112.
Merlini G., Bellotti V. Molecular mechanisms of amyloidosis. N. Engl. J. Med. 2003, 349:583-596.
Chiti F., Dobson C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 2006, 75:333-366.
Bucciantini M., Giannoni E., Chiti F., Baroni F., Formigli L., Zurdo J., et al. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002, 416:507-511.
Silveira J.R., Raymond G.J., Hughson A.G., Race R.E., Sim V.L., Hayes S.F., Caughey B. The most infectious prion protein particles. Nature 2005, 437:257-261.
Campioni S., Mannini B., Zampagni M., Pensalfini A., Parrini C., Evangelisti E., et al. A causative link between the structure of aberrant protein oligomers and their toxicity. Nat. Chem. Biol. 2010, 6:140-147.
Lashuel H.A., Hartley D., Petre B.M., Walz T., Lansbury P.T. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 2002, 418:291.
Stefani M., Dobson C.M. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 2003, 81:678-699.
Kayed R., Head E., Thompson J.L., McIntire T.M., Milton S.C., Cotman C.W., Glabe C.G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003, 300:486-489.
Meyer-Luehmann M., Spires-Jones T.L., Prada C., Garcia-Alloza M., de Calignon A., Rozkalne A., et al. Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer's disease. Nature 2008, 451:720-724.
Engel M.F., Khemtémourian L., Kleijer C.C., Meeldijk H.J., Jacobs J., Verkleij A.J., et al. Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane. Proc. Natl Acad. Sci. USA 2008, 105:6033-6038.
Xue W.F., Hellewell A.L., Gosal W.S., Homans S.W., Hewitt E.W., Radford S.E. Fibril fragmentation enhances amyloid cytotoxicity. J. Biol. Chem. 2009, 284:34272-34282.
Falsig J., Nilsson K.P., Knowles T.P., Aguzzi A. Chemical and biophysical insights into the propagation of prion strains. HFSP J. 2008, 2:332-341.
Aguzzi A., Heikenwalder M., Polymenidou M. Insights into prion strains and neurotoxicity. Nat. Rev., Mol. Cell Biol. 2007, 8:552-561.
Jiménez J., Nettleton E.J., Bouchard M., Robinson C.V., Dobson C.M., Saibil H. The protofilament structure of insulin amyloid fibrils. Proc. Natl Acad. Sci. USA 2002, 99:9196-9201.
Zurdo J., Guijarro J.I., Jiménez J.L., Saibil H.R., Dobson C.M. Dependence on solution conditions of aggregation and amyloid formation by an SH3 domain. J. Mol. Biol. 2001, 311:325-340.
Petkova A.T., Leapman R.D., Guo Z., Yau W.M., Mattson M.P., Tycko R. Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils. Science 2005, 307:262-265.
Meinhardt J., Sachse C., Hortschansky P., Grigorieff N., Fändrich M. Aβ(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibrils. J. Mol. Biol. 2009, 386:869-877.
Gosal W.S., Morten I.J., Hewitt E.W., Smith D.A., Thomson N.H., Radford S.E. Competing pathways determine fibril morphology in the self-assembly of β(2)-microglobulin into amyloid. J. Mol. Biol. 2005, 351:850-864.
Krishnan R., Lindquist S.L. Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 2005, 435:765-772.
Heise H., Hoyer W., Becker S., Andronesi O.C., Riedel D., Baldus M. Molecular-level secondary structure, polymorphism, and dynamics of full-length β-synuclein fibrils studied by solid-state NMR. Proc. Natl Acad. Sci. USA 2005, 102:15871-15876.
Dumoulin M., Kumita J.R., Dobson C.M. Normal and aberrant biological self-assembly: insights from studies of human lysozyme and its amyloidogenic variants. Acc. Chem. Res. 2006, 39:603-610.
Merlini G., Bellotti V. Lysozyme: a paradigmatic molecule for the investigation of protein structure, function and misfolding. Clin. Chim. Acta 2005, 357:168-172.
Pepys M.B., Hawkins P.N., Booth D.R., Vigushin D.M., Tennent G.A., Soutar A.K., et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature 1993, 362:553-557.
Booth D.R., Sunde M., Bellotti V., Robinson C.V., Hutchinson W.L., Fraser P.E., et al. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 1997, 385:787-793.
Dumoulin M., Last A.M., Desmyter A., Decanniere K., Canet D., Larsson G., et al. A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme. Nature 2003, 424:783-788.
Sunde M., Serpell L.C., Bartlam M., Fraser P.E., Pepys M.B., Blake C.C. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Mol. Biol. 1997, 273:729-739.
Fändrich M., Dobson C.M. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J. 2002, 21:5682-5690.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65:55-63.
Glabe C.G. Structural classification of toxic amyloid oligomers. J. Biol. Chem. 2008, 283:29639-29643.
Sunde M., Blake C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 1997, 50:123-159.
Knowles T.P., Fitzpatrick A.W., Meehan S., Mott H.R., Vendruscolo M., Dobson C.M., Welland M.E. Role of intermolecular forces in defining material properties of protein nanofibrils. Science 2007, 318:1900-1903.
Semisotnov G.V., Rodionova N.A., Razgulyaev O.I., Uversky V.N., Gripas' A.F., Gilmanshin R.I. Study of the "molten globule" intermediate state in protein folding by a hydrophobic fluorescent probe. Biopolymers 1991, 31:119-128.
Cardamone M., Puri N.K. Spectrofluorimetric assessment of the surface hydrophobicity of proteins. Biochem. J. 1992, 282:589-593.
Kremer I., Rietschel M., Dobrusin M., Mujaheed M., Murad I., Blanaru M., et al. No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population. Am. J. Med. Genet. 2000, 96:778-780.
Tanaka M., Chien P., Naber N., Cooke R., Weissman J.S. Conformational variations in an infectious protein determine prion strain differences. Nature 2004, 428:323-328.
Tanaka M., Collins S.R., Toyama B.H., Weissman J.S. The physical basis of how prion conformations determine strain phenotypes. Nature 2006, 442:585-589.
Myers S.L., Jones S., Jahn T.R., Morten I.J., Tennent G.A., Hewitt E.W., Radford S.E. A systematic study of the effect of physiological factors on β2-microglobulin amyloid formation at neutral pH. Biochemistry 2006, 45:2311-2321.
Bellotti V., Chiti F. Amyloidogenesis in its biological environment: challenging a fundamental issue in protein misfolding diseases. Curr. Opin. Struct. Biol. 2008, 18:771-779.
Sawaya M.R., Sambashivan S., Nelson R., Ivanova M.I., Sievers S.A., Apostol M.I., et al. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 2007, 447:453-457.
Wasmer C., Soragni A., Sabaté R., Lange A., Riek R., Meier B. Infectious and noninfectious amyloids of the HET-s(218-289) prion have different NMR spectra. Angew. Chem. Int. Ed. 2008, 47:5839-5841.
Nekooki-Machida Y., Kurosawa M., Nukina N., Ito K., Oda T., Tanaka M. Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity. Proc. Natl Acad. Sci. USA 2009, 106:9679-9684.
Karpinar D.P., Balija M.B., Kügler S., Opazo F., Rezaei-Ghaleh N., Wender N., et al. Pre-fibrillar β-synuclein variants with impaired β-structure increase neurotoxicity in Parkinson's disease models. EMBO J. 2009, 28:3256-3268.
Cheon M., Chang I., Mohanty S., Luheshi L.M., Dobson C.M., Vendruscolo M., Favrin G. Structural reorganisation and potential toxicity of oligomeric species formed during the assembly of amyloid fibrils. PLoS Comput. Biol. 2007, 3:1727-1738.
Orte A., Birkett N.R., Clarke R.W., Devlin G.L., Dobson C.M., Klenerman D. Direct characterization of amyloidogenic oligomers by single-molecule fluorescence. Proc. Natl Acad. Sci. USA 2008, 105:14424-14429.
Carulla N., Zhou M., Arimon M., Gairí M., Giralt E., Robinson C.V., Dobson C.M. Experimental characterization of disordered and ordered aggregates populated during the process of amyloid fibril formation. Proc. Natl Acad. Sci. USA 2009, 106:7828-7833.
Chatani E., Lee Y.H., Yagi H., Yoshimura Y., Naiki H., Goto Y. Ultrasonication-dependent production and breakdown lead to minimum-sized amyloid fibrils. Proc. Natl Acad. Sci. USA 2009, 106:11119-11124.
Collins S.R., Douglass A., Vale R.D., Weissman J.S. Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLoS Biol. 2004, 2:1582-1590.
Knowles T., Waudby C., Devlin G., Cohen S., Aguzzi A., Vendruscolo M., et al. An analytical solution to the kinetics of breakable filament assembly. Science 2009, 326:1533-1537.
Ecroyd H., Carver J.A. Unraveling the mysteries of protein folding and misfolding. IUBMB Life 2008, 60:769-774.
Kumita J.R., Johnson R.J., Alcocer M.J., Dumoulin M., Holmqvist F., McCammon M.G., et al. Impact of the native-state stability of human lysozyme variants on protein secretion by Pichia pastoris. FEBS J. 2006, 273:711-720.
Gill S.C., von Hippel P.H. Calculation of protein extinction coefficients from amino acid sequence data. Anal. Biochem. 1989, 182:319-326.
Han J.C., Han G.Y. A procedure for quantitative-determination of tris(2-carboxyethyl)phosphine, an odorless reducing agent more stable and effective than dithiothreitol. Anal. Biochem. 1994, 220:5-10.
Riddles P.W., Blakeley R.L., Zerner B. Ellman's reagent: 5,5′-dithiobis(2-nitrobenzoic acid)-a reexamination. Anal. Biochem. 1979, 94:75-81.
Serpell L.C., Berriman J., Jakes R., Goedert M., Crowther R.A. Fiber diffraction of synthetic β-synuclein filaments shows amyloid-like cross-β conformation. Proc. Natl Acad. Sci. USA 2000, 97:4897-4902.