Amyloid fibril formation

Diamant S, Podoly E, Friedler A et al (2006) Butyrylcho-linesterase attenuates amyloid fibril formation in vitro. Proc Natl Acad Sci USA 103(23) 8628-8633... 

Entry Peptide Xg X3 X4 Total charge at neutral pH Amyloid fibril formation... 

Makin OS, Atkins E, Sikorski P et al (2005) Molecular basis for amyloid fibril formation and stability. Proc Natl Acad Sci 102 315-320... 

Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchettini JC, Kelly JW. Inhibiting transthyretin conformation changes that lead to amyloid fibril formation. Proc Natl Acad Sci USA 1998 95 12956-12960. 

Lashuel HA, Lai Z, Kelly JW. Characterization of the transthyretin acid denaturation pathways by analytical ultracentrifugation implications for wild-type, V30M, and L55P amyloid fibril formation. Biochemistry 1998 37 17851-17864. 

Bonifacio MJ, Sakaki Y, Saraiva MJ. In vitro amyloid fibril formation from transthyretin the influence of ions and the amyloidogenicity of TTR variants. Biochim Biophys Acta 1996 1316 35 42. 

Jarrett JT, Lansbury PT Jr. Amyloid fibril formation requires a chemically discriminating nucleation event studies of an amyloidogenic sequence from the bacterial protein OsmB. Biochemistry 1992 31 12345-12352. 

LeVine H III. Screening for pharmacologic inhibitors of amyloid fibril formation. Methods Enzymol 1999 309 467 176. 

D. Protein Misfolding and Disease Amyloid Fibril Formation. 82... 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

It has been suggested recently that PPII helix may be the killer conformation in such diseases (Blanch et al., 2000). This was prompted by the observation, described in Section III,B, of a positive band at 1318 cm-1, not present in the ROA spectrum of the native state, that dominates the ROA spectrum of a destabilized intermediate of human lysozyme (produced by heating to 57°C at pH 2.0) that forms prior to amyloid fibril formation. Elimination of water molecules between extended polypeptide chains with fully hydrated 0=0 and N—H groups to form... 

Inhibition of amyloid fibril formation Early experimental studies... 

Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., Dyda, F., Reed,J., and Tycko, R. (2000). Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer s beta-amyloid peptide, and structural characterization by solid state NMR. Biochemistry 39, 13748-13759. 

The model of amyloid fibril formation is a nucleation step followed by growth, where the nucleation mechanism dictates the concentration and time dependence of the aggregation (Harper and Lansbury, 1997 ... 

Inoue et al. (2003) found that silk proteins will form rodlike structures and that those structure will assemble into comblike or fabric-like superstructure. The scale differences between the rods (nanometers) and the superstructure (micrometers) would suggest that the rod formation is governed by amyloid fibril formation and that the supramolecular arrangement is governed by the properties of the rod (Oroudjev et al., 2002 Putthanarat et al., 2000), namely surface interaction and hydration. Three levels of association could be considered (i) within the proteins internal /1-strands will organize to form intra /1-sheet structures, (ii) /1-sheets from neighboring molecules will associate to form fibril subunits, and (iii) the fibril subunits will further associate to form larger fibrils or rods. 

Papanikolopoulou, K., Schoehn, G., Forge, V., Forsyth, V. T., Riekel, C., Hernandez, J.-F., Ruigrok, W. H., and Mitraki, A. (2005). Amyloid fibril formation from sequences of a natural jS-structured fibrous protein, the adenovirus fiber. J. Biol. Chem. 280, 2481-2490. 

Reches, M., Porat, Y., and Gazit, E. (2002). Amyloid fibril formation by pentapeptide and tetrapeptide fragments of human calcitonin./. Biol. Chem. 277, 35475-35480. 

Unfortunately, the description of amyloid fibrils given above is simplistic since in vitro self-assembly of amyloid peptides and proteins yields polymorphic structures, as has been commonly observed in the past for other protein assemblies such as actin filaments (Millonig et al, 1988) and intermediate filaments (Herrmann and Aebi, 1999). On the one hand, assembly polymorphism complicates the characterization of fibril structure. On the other hand, it offers some insight into fibril formation. For this reason a more rational understanding of amyloid fibril formation at the molecular level is a key issue in the field of amyloidosis. 

Goldsbury, C., Goldie, K., Pellaud,J., Seelig,J., Frey, P., Muller, S. A., Kisder, J., Cooper, G. J., and Aebi, U. (2000a). Amyloid fibril formation from full-length and fragments of amylin./. Struct. Biol. 130, 352-362. 

D domain swapping shares several features with amyloid fibril formation. It is specific in that only one type of protein is contained in any given... 

The extreme stability of amyloid and amyloid-like fibrils is difficult to understand in terms of the three classes of fibril models. For the Refolding models, it has been suggested that the amyloid conformation is a default conformation for a polypeptide chain (Dobson, 1999). However, these models do not give a clear indication of what types of interactions differ in the amyloid conformation versus the native conformation, and so it is unclear why the amyloid conformation should be more stable. Also, it seems that the elevated protein concentrations associated with fibril formation might disproportionately favor nonspecific aggregation of the destabilized intermediate over amyloid fibril formation. 

Gorevic, P. D., Castano, E. M., Sarma, R., and Frangione, B. (1987). Ten to fourteen residue peptides of Alzheimer s disease protein are sufficient for amyloid fibril formation and its characteristic x-ray diffraction pattern. Biochem. Biophys. Res. Commun. 147, 854-862. 

Ivanova, M. I., Gingery, M., Whitson, L. J., and Eisenberg, D. (2003). Role of the C-terminal 28 residues of beta2-microglobulin in amyloid fibril formation. Biochemistry 42, 13536-13540. 

Nilsson, M., Wang, X., Rodziewicz-Motowidlo, S., Janowski, R., Lindstrom, V., Onnerfjord, P., Westermark, G., Grzonka, Z., Jaskolski, M., and Grubb, A. (2004). Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C Use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C.J. Biol. Chem. 279, 24236- 24245. 

Use of the anionic CP allowed for detection of amyloid fibril formation in both bovine insulin and chicken lysozyme proteins (Fig. 16). The polymer in buffer... 

Fig. 16 (a) Description of the detection of amyloid fibrils in proteins with an anionic conjugated polymer, PTAA. (b) Emission spectra (bottom) of PTAA-Native bovine insulin (filled square) and PTAA-amyloid fibrillar bovine insulin (x). (c) Kinetics of insulin amyloid fibril formation monitored by PTAA fluorescence [29]... 

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