ABSTRACT
Heparan sulfate (HS) promotes AA-amyloidogenesis by binding to serum amyloid A (SAA) and causing it to refold and assemble into AA-fibrils. In a cell culture model of AA-amyloidogenesis a peptide (33-mer) corresponding this later sequence could increase the amyloid-load by up to 180 percent. The pro-amyloidogenic activity of the 33-mer is sequence specific and dependent on His36. A 33-mer based on the SAA1.1 sequence promoted amyloidogenesis to a much higher level than the 33-mer for SAA2.1. The mechanism of action for the 33-mer is currently under investigation. The 33-mer blocks SAA binding to cells suggesting that this domain of SAA may be a binding site for an unidentified cell surface receptor. It is conceivable that the interaction with HS results in a conformational change in the 33-mer, perhaps to increase beta-sheet conformation mimicing the conformational features of amyloid enhancing factor.
