Aggregates of polypeptides

Gastric or intestinal digestion Cellular protein turnover Post-mortem tenderization of meat Aggregation of polypeptide chains Blood clotting Activation of precursors Complement action Cleavage of presecretory proteins... 

The formation of fibrillar deposits (also termed amyloids) due to the mis-folding and subsequent aggregation of polypeptides has been of recent inter-... 

The main toxic pore forming component of P. marmoratus secretion, named pardaxin, was isolated by liquid column chromatography (5). Originally two toxic (5) polypeptides, Pardaxin I and II, were isolated. However, their primary sequences have been found to be identical (6) therefore, the two components most probably represent different aggregates of one polypeptide. This finding is in contrast to the secretion of P. pavonicuSj which contains three toxic polypeptides (8). Pardaxin is a single chain, acidic, amphipathic, hydrophobic polypeptide, composed of 33 amino acids and with a mass around 3500 daltons (5,6). The primary sequence is (6) NHj-Gly-Phe-Phe-Ala-Leu-Ile-Pro-Lys-Ile-Ile-Ser-Ser-Pro-Ile-Phe-Lys-Thr-Leu-Leu-Ser-Ala-Val-Gly-Ser-Ala-Leu-Ser-Ser-Ser-Gly-Gly-Gln-Glu-COOH. 

Disulfide exchange can also sometimes occur, and prompt a reduction in biological activity (Figure 6.21). Intermolecular disulfide exchange can result in aggregation of individual polypeptide molecules. 

Speed, M. A., Wang, D. I. C., and King, J. (1996). Specific aggregation of partially folded polypeptide chains The molecular basis of inclusion body composition. Nat. Biotechnol. 14, 1283-1287. 

The extreme stability of amyloid and amyloid-like fibrils is difficult to understand in terms of the three classes of fibril models. For the Refolding models, it has been suggested that the amyloid conformation is a default conformation for a polypeptide chain (Dobson, 1999). However, these models do not give a clear indication of what types of interactions differ in the amyloid conformation versus the native conformation, and so it is unclear why the amyloid conformation should be more stable. Also, it seems that the elevated protein concentrations associated with fibril formation might disproportionately favor nonspecific aggregation of the destabilized intermediate over amyloid fibril formation. 

Cells have developed a sophisticated system of molecular chaperones and proteases to reduce the amount of unfolded or aggregated proteins (Wickner et al. 1999). Chaperones recognize hydrophobic stretches of polypeptides that become surface exposed as a consequence of misfolding or unfolding. If refolding attempts fail, irreversibly damaged polypeptides are removed by proteases. 

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