Human amylin formed

Human amylin, or islet amyloid polypeptide (hlAPP), is a 37-residue peptide hormone which forms both intracellular and extracellular (EC) amyloid deposits in the pancreas of most type II diabetic subjects. The core of the structure in the SDS micelle is an ot-helix that runs from about residues 5-28. Although the basic structural unit in the fibrils in... 

Fig. 1. Structure of amyloid fibrils formed by the human amylin peptide. Negatively stained (A) and metal shadowed (B) fibrils formed by human amylin (adapted from Goldsbury et al., 2000a). (C) A human amylin fibril model formed by three protofibrils having a superpleated /i-structure (adapted from Kajava et al., 2005). Only Ca traces of the polypeptide chains are shown. (D) Atomic model of the cross-/ motif formed by the human amylin peptide (adapted from Kajava et al, 2005). Scale bar, 100 nm (A and B).

For A/i it is worth noting that while single 5-nm protofibrils were rarely imaged by EM or SFM, the thinnest single fibrils had a diameter around 8-9 nm and were termed protofibrils by many researchers in the field (Goldsbury et al., 2005 Harper et al., 1997, 1999 Lambert et al, 1998 Nielsen et al., 1999 Walsh et al., 1997, 1999). Flat and twisted ribbons formed from 5-nm-wide subunits, as seen with human amylin, were also depicted for AjSi 4o (Fig- 2G Goldsbury et al., 2000b, 2005). 

A/1 it was possible to follow the growth of twisted ribbons, with a periodic twist of 80-130 nm, by depositing seeds on mica prior to the injection of a fresh peptide solution (Fig. 4C Goldsbury et al., 2005). In the case of human amylin, it was even possible to observe by time-lapse SFM how fibrils are formed from an oligomeric nucleus by initial growth in height from... 

Green, J. D., Goldsbury, C., Mini, T., Sundetji, S., Frey, P., Kisder, J., Cooper, G., and Aebi, U. (2003). Full-length rat amylin forms fibrils following substitution of single residues from human amylin./. Mol. Biol. 326, 1147-1156. 

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. 

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