Amyloid structural studies

IV. Recent Advances in Structural Studies of Amyloid and Prion Fibrils. 10... 

The contributions to this volume demonstrate that structural studies of fibrous /1-proteins, as well as prion and amyloid fibrils, have advanced rapidly thanks in large part to improved experimental techniques and better theoretical analysis of the ever-increasing structural data. It is also possible to learn from studies of naturally occurring silks (Dicko et al., this volume) howvariations in the conditions of production of silk threads from the same protein can produce a variety of /1-structures with very distinct... 

Jimenez, J. L., Tennent, G., Pepys, M., and Saibil, H. R. (2001). Structural diversity of ex vivo amyloid fibrils studied by cryo-electron microscopy. /. Mol. Biol. 311, 241-247. 

Structural and dynamic features of Alzheimer s Aft peptide in amyloid fibrils studied by site-directed spin labeling./. Biol. Chem. 277, 40810-40815. 

Torok, M., Milton, S., Kayed, R., Wu, P., Mclntire, T., Glabe, C. G., and Langen, R. (2002). Structural and dynamic features of Alzheimer s Abeta peptide in amyloid fibrils studied by site-directed spin labeling. / Biol. Chem. 277, 40810-40815. 

Modifications introduced by the mutations were central to the alteration of the specificities of the enzymes studied, which were capable of cleaving (3-casein at many new sites, for example, hydrolyzing the fragment Argl-Lysl05, reported to be a trypsin inhibitor (Bouhallab et al, 1997). Since many tryptic inhibitors contain amidated Glu and Asp, and form amyloid structures, the mutants of this type could be used for the hydrolysis of the lytically resistant protein structures. 

Huang THJ, et al. Structural studies of soluble oligomers of the alzheimer (beta)-amyloid peptide. J. Molec. Biol. 2000 297 73. 

Structural Studies with rPrP Amyloid Fibrils. 150... 

Sun Y, Breydo L, Makarava N, Yang Q, Bocharova OV, Baskakov IV (2007) Site-specific conformational studies of prion protein (PrP) amyloid fibrils revealed two cooperative folding domains within amyloid structure. J Biol Chem 282 9090-9097... 

Beel AJ, Mobley CK, Kim HJ, et al. Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP) does APP function as a cholesterol sensor Biochemistry. 2008 47(36) 9428-9446. 

A field of research, on which solid-state NMR spectroscopy had a tremendous impact during the past decade, is the structural study of amyloid fibrils. Solid-state NMR spectroscopy can provide information on several aspects of the cross-p core structure of amyloid fibrils such as the localization of p-strands within the amino acid sequence and their relative arrangement within protofilaments and at the protofilament interface. Even high-resolution structures for the fibril core have been determined. An overview over emerging central motifs for amyloid structure is given in Fig. 4. 

Shiv]i A P, Brown F, Davies M C, Jennings K H, Roberts C J, Tendler S J B, Wilkinson M J and Williams P M 1995 Scanning tunnelling microscopy studies of p-amyloid fibril structure and assembly FEBS Lett. 371 25-8... 

Progress in deducing more structural details of these fibers has instead been achieved using NMR, electron microscopy and electron diffraction. These studies reveal that the fibers contain small microcrystals of ordered regions of the polypeptide chains interspersed in a matrix of less ordered or disordered regions of the chains (Eigure 14.9). The microcrystals comprise about 30% of the protein in the fibers, are arranged in p sheets, are 70 to 100 nanometers in size, and contain trace amounts of calcium ions. It is not yet established if the p sheets are planar or twisted as proposed for the amyloid fibril discussed in the previous section. 

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