Fibrillar amyloid structure

Farrell HM Jr, Cooke PH, Wickham ED, Piotrowski EG, Hoagland PD (2003) Environmental influences on bovine kappa-casein reduction and conversion to fibrillar (amyloid) structures. J Protein Chem 22 259-... 

Just like in coiled-coils, p-sheet secondary structure (Fig. 2) is ubiquitous in natural examples and in proteins and biomaterials. Alzheimer s disease is characterized by fibrillar amyloid plaques in the cerebral parenchyma. The insoluble amyloid fibrils are predominantly formed upon conformational switching of the 42 amino acid... 

Lesions of Alzheimer s disease, evident as dense plaques composed of fibrillar amyloid beta-proteins, likely develop when these proteins are first induced to form beta-sheet secondary structures. It was demonstrated that membranes containing oxidatively damaged phospholipids accumulated amyloid beta-protein significantly faster than membranes containing unoxidized phospholipids. The protein on oxidized membranes more readily changed conformation to a beta-sheet, indicating that oxidatively damaged phospholipid membranes... 

Jayasinghe, S. A., and Langen, R. (2004). Identifying structural features of fibrillar islet amyloid polypeptide using site-directed spin labeling. J. Biol. Chem. 279, 48420-48425. 

What is the nature of the insoluble forms of the prion protein They are hard to study because of the extreme insolubility, but the conversion of a helix to (3 sheet seems to be fundamental to the process and has been confirmed for the yeast prion by X-ray diffraction.11 It has been known since the 1950s that many soluble a-helix-rich proteins can be transformed easily into a fibrillar form in which the polypeptide chains are thought to form a P sheet. The chains are probably folded into hairpin loops that form an antiparallel P sheet (see Fig. 2-ll).ii-11 For example, by heating at pH 2 insulin can be converted to fibrils, whose polarized infrared spectrum (Fig. 23-3A) indicates a cross-P structure with strands lying perpendicular to the fibril axis >mm Many other proteins are also able to undergo similar transformation. Most biophysical evidence is consistent with the cross-P structure for the fibrils, which typically have diameters of 7-12 rnn."-11 These may be formed by association of thinner 2 to 5 nm fibrils.00 However, P-helical structures have been proposed for some amyloid fibrils 3 and polyproline II helices for others. 1 11... 

Another approach toward fibrillar nanowires has been taken by Baldwin and colleagues (2006), who assembled a porphyrin binding protein onto the surface of an amyloid fibril. This binding protein could incorporate heme to form a functional b-type cytochrome. These fibrils could be developed to create wires for electron transfer, similar to structures observed in nature that consist of chains of heme molecules. 

The protein elastin presents another opportunity to create amyloid-like fibrils from natural proteins for the purpose of developing biomaterials. Elastin is found in tissue where it imparts elastic recoil, and fibrils formed from this protein may demonstrate some of the elastic properties of the constituent elastic proteins (Bochicchio et al., 2007). Elastin typically contains the sequence poly(ZaaGlyGlyYaaGly) (where Zaa, Yaa = Val or Leu) (Tamburro et al., 2005), and short stretches of the protein retain the ability to form structures similar to the original protein. Simple proline to glycine mutations in the hydrophobic domains of elastin can induce the formation of amyloid-like fibrils (Miao et al., 2003), suggesting that fibrillar materials can be easily generated from these sequences. 

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