Proteins, classes fibrillar

The amyloidoses are a class of conformational diseases that arise from the conversion of normally unfolded or globular proteins into fibrillar aggregates that are either pathogenic or non-functional. At present there are more than 20 proteins that are associated with human amyloid diseases. This review focuses on three natively unfolded proteins that form fibrillar aggregates amyloid-, islet amyloid polypeptide ( amylin ), and a-synuclein, the diseases they contribute to and chemical and biophysical approaches that are used to investigate these proteins aggregation. 

In vitro, fibril formation by several proteins displays an initial lag phase, followed by a rapid increase in aggregation (reviewed in Rochet and Lansbury, 2000). Introduction of fibrillar seeds eliminates the lag phase. These cooperative aggregation kinetics suggest that fibril formation begins with the formation of a nucleus and proceeds by fibril extension. The structure of the nucleus must therefore act as a template for the protein s conformation in the fibril. As the structural requirements for templating are unclear, it is difficult to assess the consistency of the model classes with this feature of fibril formation. We have described one possible templating mechanism for the cross-/ spine of GNNQQNY (Nelson et al., 2005). 

More recently, the issue of in situ forming fibrillar matrices has been tackled with the development of self-assembling synthetic peptides. Two main classes of such peptides can be recognized the first one takes inspiration from the association properties of amyloid protein, with a self-assembly primarily based on the formation of /3-sheets and on hydrophobic association this latter feature is often obtained by alternating ionic and hydrophobic aminoacidic residues, although the presence of hydrophobic end-groups can promote similar effects. ... 

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