Atomic amyloid formation

Huff, M. E., Balch, W. E., and Kelly, J. W. (2003). Pathological and functional amyloid formation orchestrated by the secretory pathway. Curr. Opin. Struct. Biol. 13, 674-682. Jansen, R., Dzwolak, W., and Winter, R. (2005). Amyloidogenic self-assembly of insulin aggregates probed by high resolution atomic force microscopy. Biophys. J. 88, 1344-1353. 

Harper JD, Lieber CM, Lansbury PT Jr. Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer s disease amyloid-beta protein. Chem Biol 1997 4 951-959. 

Kowalewski T, Holtzman DM. In situ atomic force microscopy study of Alzheimer s beta-amyloid peptide on different substrates new insights into mechanism of beta-sheet formation. Proc Natl Acad USA 1999 96 3688-3693. 

These three examples emphasize the idea that a complete description of amyloid fibril polymorphisms will only be achieved when 3D structures at atomic detail become available (Luhrs et al., 2005). Last but not least, since the various morphologies observed for amyloid fibrils are defining the end point of the assembly process, an essential need is to properly define the early stages of fibril formation, namely the oligomeric states of the peptide or protein in solution prior to assembly into fibrils. 

The same approach was used to study the reductive modification of a methionine residue (Met ) in the amyloid-/ peptide [A/ (l-40)] and its reversed sequence [A/ (40-l)]. The A/3 peptide suffers the highly selective attack of H atoms on the Met residue, with the formation of a modified peptide containing an a-amino-butyric acid residue. Formation of tw -lipids in POPC system as a marker of radical damage to A/3 peptide clearly shows the transfer of radical damage from the peptide to the lipid domain. 

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