Amyloid-like fibrils

Nelson, R., Sawaya, M. R., Balbirnie, M., Madsen, A. O., Riekel, C., Grothe, R., and Eisenberg, D. (2005). Structure of the cross-beta spine of amyloid-like fibrils. Nature 435, 773-778. 

Wang, W., and Hecht, M. H. (2002). Rationally designed mutations convert de novo amyloid-like fibrils into monomeric beta-sheet proteins. Proc. Natl. Acad. Sri. USA 99, 2760-2765. 

Dos Reis, S., Coulary-Salin, B., Forge, V., Lascu, I., Begueret,J., and Saupe, S. J. (2002). The HET-s prion protein of the filamentous fungus Podospora anserina aggregates in vitro into amyloid-like fibrils. J. Biol. Chem. 277, 5703—5706. 

Kirschner, D. A., Inouye, H., Duffy, L. K., Sinclair, A., Lind, M., and Selkoe, D. J. (1987). Synthetic peptide homologous to fS protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc. Natl. Acad. Sci. USA 84, 6953-6957. 

Maji, S. K., Haidar, D., Drew, M. G. B., Banerjee, A., Das, A. K., and Banerjee, A. (2004). Self-assembly of /1-turn forming synthetic tripeptides into supramolecular //-sheets and amyloid-like fibrils in the solid state. Tetrahedron 60, 3251-3259. 

Cardoso, I., Goldsbury, C. S., Muller, S. A., Olivieri, V., Wirtz, S., Damas, A. M., Aebi, U., and Saraiva, M. J. (2002). Transthyretin fibrillogenesis entails the assembly of monomers A molecular model for in vitro assembled transthyretin amyloid-like fibrils./. Mol. Biol. 317, 683-695. 

Goldsbury, C., Aebi, U., and Frey, P. (2001). Visualizing the growth of Alzheimer s A beta amyloid-like fibrils. Trends Mol. Med. 7, 582. 

Higham, C. E., Jaikaran, E. T., Fraser, P. E., Gross, M., and Clark, A. (2000). Preparation of synthetic human islet amyloid polypeptide (LAPP) in a stable conformation to enable study of conversion to amyloid-like fibrils. FEBS Lett. 470, 55-60. 

Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble proteins. Both of these groups of fibrils, despite differences in the sequence and native structure of their component proteins, share common... 

Fig. 2. Classes of structural models of amyloid-like fibrils. The Refolding models propose that a native protein (circle) partially or completely unfolds to attain a new fold (rectangle) in the fibril (stack of rectangles). In contrast, the Gain-of-Interaction models propose that only part of the native protein changes and takes on a new structure in the fibril. The remainder of the protein (partial circle) retains its native structure. The Natively Disordered models begin with disordered proteins or protein fragments, and these become ordered in the fibril. PolyQ refers to polyglutamine.

Fig. 3. Refolding model of insulin protofilaments, from Jimenez et al. (2002). (A) Ribbon diagram of the crystal structure of porcine insulin (PDB ID code 3INS), generated with Pymol (DeLano, 2002). The two chains are shown as dark and light gray with N- and C-termini indicated. The dotted lines represent the three disulfide bonds 1 is the intrachain and 2 and 3 are the interchain bonds. (B) Cartoon representation of the structure of monomeric insulin in the fibril, as proposed by Jimenez et al. (2002). The thick, arrowed lines represent /1-strands, and thinner lines show the remaining sequence. The disulfide bonds are as represented in panel A, and N- and C-termini are indicated. (Components of this panel are not to scale.) (C) Cartoon representation of an insulin protofilament, showing a monomer inside. The monomers are proposed to stack with a slight twist to form two continuous /(-sheets. (Components of this panel, including the protofilament twist, are not to scale.) In the fibril cross sections presented byjimenez et al. (2002), two, four, or six protofilaments are proposed to associate to form the amyloid-like fibrils.

A cross-jS spine model was proposed for the fibril structure of human /]2-microglobulin (h/]2m) (Ivanova et al., 2004). h/I2m is a 99-amino acid serum protein with a 7-stranded /(-sandwich fold (Fig. 10A Saper et al, 1991). In patients on long-term kidney dialysis, the protein is deposited as amyloid fibrils in the joints (Floege and Ehlerding, 1996 Koch, 1992). In vitro-formed fibrils of h/)2m give a cross-/] X-ray diffraction pattern (Ivanova et al., 2004 Smith et al., 200S). Several studies have shown that segments of h/]2m form amyloid-like fibrils on their own (Ivanova et al., 2003 Jones et al., 2003 Kozhukh et al, 2002). 

Fig. 16. Parallel superpleated /J-structure proposed for Ure2p amyloid-like fibrils, from Kajava et al. (2004). (A) Ribbon diagram o( a dimer of Saccharnmyces cermnsiae l Jre2p C-terminal domains (PDB ID code 1G6W), generated with Pymol (DeLano, 2002). The monomers are colored in light and dark gray and are viewed down the twofold symmetry axis. The N- and C-termini are indicated, and residue 137 is denoted by an open arrow.

C) Cross section of the Ure2p amyloid-like fibril model, showing the parallel superpleated -structure at the N-terminus, and various positions possibly occupied by the globular C-terminus (gray ovals). Panels B and C are based on Fig. 4 of Kajava et al. (2004). 

In this model (Fay et al., 2005), portions of the N- and C-terminal regions, specifically residues 6 and 137, are in close proximity in the fibril, and the C-terminal domain retains a native-like structure. There is evidence that this non-amyloid-like fibril can convert to the cross-/ -containing filament with heat treatment, incubation at low pH (Bousset et al., 2003), or extensive drying (Fay et al., 2005), but it is unclear what sort of structural change might link the two fibril types. 

Consistencies of the Three Model Classes with the Common Properties of Amyloid-like Fibrils"... 

The Refolding, Gain-of-Interaction, and Natively Disordered classes of fibril models are at least partly consistent with the common properties of amyloid and amyloid-like fibrils. We summarize consistencies, inconsistencies, and uncertainties linking model class and amyloid property in Table I. In the following paragraphs, we describe these properties and discuss the extent to which they may be explained by the various classes of models. 

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